hematopoiesis histology - maha hammady.pptx

hematopoiesis histology—Maha Hammady.

1. Maha Hammady,MBBCh,MMSc

2. hematopoiesis By/ Maha Hammady Hemdan MBBCh- MMSc - Faculty of Medicine, Alexandria University. 2015

3. 3 hematopoiesis Hematopoiesis (is also called hemopoiesis, hematogenesis and hemogenesis )– the formation of blood cellular components – occurs during embryonic development (prenatal hemopoiesis) and throughout adulthood (postnatal hemopoiesis ) to produce and replenish the blood system. hemopoiesis

4. prenatal hemopoiesis

5. Prenatal Hemopoiesis Prenatally, hemopoiesis is subdivided into four phases: mesoblastic, hepatic, splenic, and myeloid. 5 phase Mesodermal phase Hepatic phase Splenic phase Myeloid phase Site the mesoderm of the yolk sac Liver Spleen Bone marrow Timing Around 2 weeks after conception 6 th week till birth 14 th week (2 nd trimester) till birth end of the 2 nd trimester till adulthood events mesenchymal cells aggregate into clusters known as blood islands . The peripheral cells of these islands form the vessel wall, and the remaining cells become erythroblasts , which differentiate into Primitive erythrocytes The circulating erythrocytes still have nuclei, and nonerythroid progenitors appear by the eighth week of gestation. As the skeletal system continues to develop, the bone marrow assumes an increasing role in blood cell formation. Cells produced Primitive erythrocytes ( nucleated erythrocytes containing HbF (fetal hemoglobin) , macrophages Erythrocytes, granulocytes, monocytes Lymphocytes All blood cell types Prenatal Hemopoiesis

6. prenatal hemopoiesis postnatal hemopoiesis Prenatal Hemopoiesis

7. Postnatal hemopoiesis

8. 8 The monophyletic theory of hemoposis The monophyletic theory of hematopoiesis suggests that all blood cells, regardless of their lineage (erythroid, myeloid, lymphoid), originate from a common precursor cell. This theory posits that there is a single, unifying lineage for hematopoiesis, and the diverse blood cell types differentiate from a shared ancestor. Key points regarding the monophyletic theory include: 1. Common Origin: According to the monophyletic theory, all blood cells, including red blood cells, white blood cells, and platelets, arise from a common hematopoietic stem cell (HSC). 2. Pluripotent Stem Cells: Hematopoietic stem cells are considered pluripotent, meaning they can give rise to a variety of differentiated cell types. 3. Lineage Commitment: The monophyletic theory acknowledges that as hematopoietic stem cells differentiate, they undergo lineage commitment, leading to the formation of distinct cell lineages such as erythroid, myeloid, and lymphoid. 4. Hierarchical Development: The theory suggests a hierarchical development of blood cells, starting from the pluripotent hematopoietic stem cell and branching into committed progenitors that eventually differentiate into specialized blood cell types. While the monophyletic theory provides a unified framework for hematopoiesis, it is essential to note that ongoing research may refine our understanding of the intricacies of blood cell development. This theory serves as a foundational concept in hematology, influencing research, diagnostics, and therapeutic interventions related to blood disorders and diseases.

9. Stem Cells, Progenitor Cells, and Precursor Cells 9 1-Stem Cells: Definition: Stem cells are undifferentiated cells with the unique ability to divide and give rise to both identical stem cells (self-renewal) and differentiated, specialized cell types. characteristics: All blood cells arise from pluripotential hemopoietic stem cells (PHSCs) (also known as hemopoietic stem cells [HSC]), which account for about 0.01% of the nucleated cell population of bone marrow. They are usually amitotic but may undergo bursts of cell division,giving rise to - more PHSCs - as well as to two types of multipotential hemopoietic stem cells (MHSCs), also known as multipotent progenitors. The two populations of MHSCs are colony-forming unit– lymphocyte (CFU-Ly), also known as common lymphoid progenitors, and CFU-GEMM ( colonyforming unit-granulocyte, erythrocyte, monocyte, megakaryocyte), also known as common myeloid progenitors. Both PHSCs and MHSCs resemble lymphocytes and constitute a small fraction of the null-cell population of circulating blood. Stem cells are commonly in the G0 stage of the cell cycle but can be driven into the G1 stage by various growth factors and cytokines.

10. Stem Cells, Progenitor Cells, and Precursor Cells 10 2- Progenitor Cells : Definition: Progenitor cells are partially differentiated cells derived from stem cells, committed to a specific lineage, and with limited differentiation potential. characteristics: - resemble small lymphocytes -They are unipotential (i.e., committed to forming single cell line, such as eosinophils). -Their mitotic activity and differentiation are controlled by specific hemopoietic factors. -These cells have only limited capacity for self-renewal.

11. Stem Cells, Progenitor Cells, and Precursor Cells 11 3- Precursor cells : Definition: Precursor cells are cells that precede the final, fully mature cell type in the process of differentiation. characteristics: -have specific morphological characteristics that permit them to be recognized as the first cell of a particular cell line. -Precursor cells undergo cell division and differentiation, eventually -giving rise to a clone of mature cells. -Incapable of self-renewal

12. 12

13. 13 Hematopoietic growth factors are signaling molecules that regulate the growth, development, and differentiation of blood cells in the process of hematopoiesis. These factors play a crucial role in maintaining a balanced and functional blood cell population. Here's a concise account: - Hematopoietic growth factors are critical for maintaining homeostasis in the blood system by regulating the production of different blood cell types. - Their therapeutic applications are widespread, including the treatment of anemia, neutropenia, and thrombocytopenia associated with various medical conditions and treatments. Hemopoietic Growth factors

14. Postnatal hemopoiesis A-Erythropoiesis

15. A-Erythropoiesis 15 A-Erythropoiesis Erythropoiesis, the formation of red blood cells, is under the control of several cytokines, namely steel factor, interleukin-3, interleukin-4, and erythropoietin

16. A-Erythropoiesis 16 1-Proerythroblast Size and Shape: - Proerythroblasts are relatively large cells, typically ranging in size from 14 to 20 micrometers in diameter. -they re the first microscopically recognizable precursor cells. - They exhibit a round or slightly oval shape. 2. Nucleus: - The nucleus of a proerythroblast is large and occupies a significant portion of the cell. - It is typically round 3. Mitotic Ability: - Proerythroblasts are actively dividing cells. They undergo several rounds of mitosis to generate a pool of cells that will further differentiate into erythrocytes. 4. Nucleoli: - many nucleoli may be visible within the nucleus of a proerythroblast reflecting the cell's high metabolic activity during this phase of erythropoiesis. 5. Cytoplasm: - The cytoplasm of proerythroblasts is light basophilic - The cytoplasm contains a developing network of organelles, including rough endoplasmic reticulum ( rER ), many polysomes and mitochonria . The proerythroblast (A) and (P) is the earliest identifiable erythroid precursor in the bone marrow. Electron micrograph of a proerythroblast, displaying its nucleus as well as the perinuclear cytoplasm. Note that the nucleoplasm is relatively smooth in appearance and that the cytoplasm is rich in mitochondria and free ribosomes, indicating that the cell is active in protein synthesis (×14000). nuc , Nucleolus.

17. A-Erythropoiesis 17 2-Basophillic erythroblast Size and Shape: -Basophilic erythroblasts are typically larger than mature red blood cells, ranging in size from 12 to 17 micrometers in diameter. -They exhibit a round or slightly oval shape, 2. Nucleus: -The nucleus of a basophilic erythroblast is relatively large and round, occupying a significant portion of the cell. -The nuclear chromatin is still visible, but it is starting to condense as the cell progresses toward maturity. 3. Mitotic Ability: -Basophilic erythroblasts retain the ability to undergo mitosis 4. Nucleoli: -One or more nucleoli may be present in the nucleus of basophilic erythroblasts; reflecting the cell's high metabolic activity during this stage of erythropoiesis. 5. Cytoplasm: - The cytoplasm of basophilic erythroblasts is basophilic - It contains a developing network of organelles, including many rough endoplasmic reticulum ( rER ), polysomes and mitochondria, crucial for hemoglobin production. -some hemoglobin is present. The basophilic erythroblast (B) Electron micrograph of a  basophilic erythroblast https://stock.adobe.com/images/basophilic-erythroblast/290399442 B

18. A-Erythropoiesis 18 3-Polychromatophilic erythroblast Size and Shape: -Polychromatophilic erythroblasts are smaller than earlier basophilic stages, typically ranging from 12 to 15 micrometers in diameter. -They exhibit a round or slightly oval shape, 2. Nucleus: -The nucleus of a polychromatophilic erythroblast is still present, but it is becoming more condensed as the cell progresses toward maturity. (checkboard pattern) -Chromatin becomes more compact 3. Mitotic Ability: -Unlike earlier stages, polychromatophilic erythroblasts have reduced mitotic activity. -The cell is shifting focus from cell division to the synthesis of hemoglobin, a process critical for the ultimate function of red blood cells. 4. Nucleoli: -Nucleoli are generally not visible in polychromatophilic erythroblasts, indicating a decrease in the synthesis of ribosomal RNA. 5. Cytoplasm: -The cytoplasm of polychromatophilic erythroblasts is described as "polychromatophilic" due to its ability to take up both acid and basic stains. - This is a result of the cell actively producing and accumulating hemoglobin, which imparts a bluish-gray tint to the cytoplasm. -Mitochondria become more prominent in the cytoplasm, supporting the energy demands associated with hemoglobin synthesis. The polychromatophilic erythroblast (p) and late polychromatophilic erythroblast (LP) , note the checkboard appearance of the nucleus P LP LP

19. A-Erythropoiesis 19 4-Orthochromatophilic erythroblast 1.Size and Shape: - Orthochromatophilic erythroblasts are relatively small, with a diameter ranging from 8 to 12 micrometers. -They exhibit a round or slightly oval shape, 2. Nucleus: -The nucleus of orthochromatophilic erythroblasts is markedly condensed and the nucleus is positioned eccentrically (or is being extruded) 3. Mitotic Ability: - Orthochromatophilic erythroblasts have lost their ability to undergo mitosis. - This irreversible exit from the cell cycle is a characteristic feature of cells committed to becoming mature red blood cells. 4. Nucleoli: -Nucleoli are entirely absent in orthochromatophilic erythroblasts, indicating a cessation of active ribosomal RNA synthesis. 5. Cytoplasm: -The cytoplasm of orthochromatophilic erythroblasts is heavily laden with hemoglobin, giving it a pinkish hue. -This stage is often referred to as the "polychromatophilic normoblast" due to the residual staining properties of the cytoplasm. LM of t he Orthochromatophilic erythroblast Electron micrograph of an orthochromatophilic erythroblast. Observe that the nucleus possesses a lot of heterochromatin

20. A-Erythropoiesis 20 4-Orthochromatophilic erythroblast 1.Size and Shape: - Orthochromatophilic erythroblasts are relatively small, with a diameter ranging from 8 to 12 micrometers. -They exhibit a round or slightly oval shape, 2. Nucleus: -The nucleus of orthochromatophilic erythroblasts is markedly condensed and the nucleus is positioned eccentrically (or is being extruded) 3. Mitotic Ability: - Orthochromatophilic erythroblasts have lost their ability to undergo mitosis. - This irreversible exit from the cell cycle is a characteristic feature of cells committed to becoming mature red blood cells. 4. Nucleoli: -Nucleoli are entirely absent in orthochromatophilic erythroblasts, indicating a cessation of active ribosomal RNA synthesis. 5. Cytoplasm: -The cytoplasm of orthochromatophilic erythroblasts is heavily laden with hemoglobin, giving it a pinkish hue. -This stage is often referred to as the "polychromatophilic normoblast" due to the residual staining properties of the cytoplasm. Electron micrograph of an orthochromatophilic erythroblast (normoblast). The cell is shown just before extrusion of the nucleus. The cytoplasm contains a group of mitochondria located below the nucleus and small cytoplasmic vacuoles. The cytoplasm is relatively dense because of its hemoglobin content. The fi ne, dense particles scattered in the cytoplasm are ribosomes. 10,000. (Courtesy of Dr. Dorothea Zucker-Franklin.)

21. https://cob.silverchair-cdn.com/cob/content_public/journal/jcs/71/1/10.1242_jcs.71.1.177/3/joces_71_1_177.pdf?Expires=1705071081&Signature=cVthPkW0fQf4o~TgQ7RbdJFbPAyBmeA5EP35360nTfM1d6lAe79yQTpeh4o~ye9RuqxkxgXBLNf812q84c7VOGOMthP2R-ZUhlHBHnex-J7pAe3qJCbrNFWFq~TcYH5sdoAhgA5DmA7v6UMSNWwyYL7bXoQ6a868MkEUqjgiJy79iilZ74n7j0onNyaVQ77QZunQLlgI9ZhE4JgC1Ek9IGlDlLC9vj9IArqT1sMvehgs5BchBtFkhxPBZL-Hku-ExnABZ9z-FplIrY4DMDxiEKr0bzwRCoYz9X4RzNhEBgGE8-WDTtrmIdeMNzBN1z2EuccFa22UHyvMlLEhtabTTQ__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA A-Erythropoiesis 21 5-Reticulocyte 1.Size and Shape: -Reticulocytes are small, with a diameter ranging from 7 to 8 micrometers. -They exhibit a round or slightly oval shape, 2. Nucleus: -Mature reticulocytes lack a nucleus, making them one of the few mammalian cells that function without a nucleus. 3. Mitotic Ability: -Reticulocytes do not have the ability to undergo mitosis as they have already exited the cell cycle during earlier stages of erythropoiesis. 4. Nucleoli: -Reticulocytes, having expelled their nucleus, also lack nucleoli. They are essentially enucleated cells 5. Cytoplasm: -The cytoplasm of reticulocytes contains remnants of ribosomal RNA, forming a network of reticulum or reticular material when stained with cresyl blue. This gives reticulocytes their name. - The cytoplasm is rich in hemoglobin -Under electron microscopy, the cytoplasm of reticulocytes shows a mesh-like appearance, representing the residual ribosomal material. -Mitochondria are still present but decrease in number compared to earlier erythroblastic stages Blood film using cresyl blue stain showing the retuclocytes Electron micrograph of a polychromatophilic erythrocyte (reticulocyte). The nucleus is no longer present, and the cytoplasm shows the characteristic fi mbriated processes that occur just after nuclear extrusion. Mitochondria are still present, as are early and late endosomes and ribosomes. 16,500.

22. A-Erythropoiesis 22 6-Mature Erythrocyte 1.Size and Shape: -Mature erythrocytes are small, with a diameter of about 7-8 micrometers. -They are biconcave discs, resembling a donut without a hole. This shape maximizes the surface area for gas exchange and flexibility to navigate through narrow capillaries. 2. Nucleus: -Mature erythrocytes lack a nucleus. The expulsion of the nucleus during the final stages of erythropoiesis increases the cell's capacity to carry oxygen and allows for a flexible and deformable shape. 3. Mitotic Ability: -Erythrocytes cannot undergo mitosis or any form of cellular division. -They are unable to repair themselves and have a finite lifespan, typically circulating for about 120 days before being removed by the spleen and liver. 4. Nucleoli: -As mature erythrocytes are devoid of a nucleus, they also lack nucleoli 5. Cytoplasm: -The cytoplasm of mature erythrocytes primarily consists of hemoglobin, the iron-containing protein responsible for oxygen binding and transport. -The absence of most organelles, including mitochondria, reduces metabolic demands, allowing the cell to focus on its oxygen-carrying function. Electron micrographs of mature erythrocytes reveal a homogenous cytoplasm with no discernible organelles. The biconcave shape is evident, maximizing the surface area-to-volume ratio for efficient gas exchange.

23. 23 The erythroblastic island. ( A ) Erythroblastic island in E13.5 fetal liver. The cytoplasmic extensions of the central macrophage (stained with the F4/80 antibody) (brown) are surrounding erythroid cells at various stages of differentiation. ( B ) Schematic drawing of an erythroblastic island. https://perspectivesinmedicine.cshlp.org/content/3/4/a011601.full A-Erythropoiesis

24. 24 A-Erythropoiesis

25. Postnatal hemopoiesis B-thrombopoiesis

26. B-thrombopoiesis 26 B-Thrombopoiesis The formation of platelets is under the control of thrombopoietin, which induces the development and proliferation of giant cells known as megakaryoblasts

27. 27 1-Megakaryoblast 1.Size and Shape: -Megakaryoblasts are relatively large cells, typically larger than other hematopoietic precursors, with a diameter ranging from 25 to 40 micrometers. - They exhibit a round or slightly oval shape. 2. Nucleus: -Megakaryoblasts have a single, large, and lobulated nucleus. -The nucleus may exhibit prominent nucleoli and is characterized by its irregular contour. 3. Mitotic Ability: -Megakaryoblasts undergo mitosis, dividing to produce more precursor cells in the megakaryocytic lineage. -They are considered the proliferative stage leading to the formation of megakaryocytes. -These cells undergo endomitosis , whereby the cell does not divide (no karyokinesis nor cytokinesis); instead, it becomes larger, and the nucleus becomes polyploid, as much as 64 N 4. Nucleoli: -Megakaryoblasts may have one or more prominent nucleoli within the nucleus. -Nucleoli are involved in ribosomal RNA synthesis, reflecting the cell's high metabolic activity during this phase of megakaryopoiesis 5. Cytoplasm: -The cytoplasm of megakaryoblasts is basophilic - It contains developing organelles, such as rough endoplasmic reticulum ( rER ), indicative of active protein synthesis, including the production of platelet components -well developed Golgi apparatus, numerous mitochondria, abundant RER, and many lysosomes B-thrombopoiesis

28. 28 1-Megakaryoblast B-thrombopoiesis

29. 29 2-Megakaryocyte 1.Size and Shape: -Megakaryocytes are among the largest cells in the bone marrow, with a diameter ranging from 30 to 100 micrometers. -They are typically multi-lobulated and have a distinctive irregular shape. 2. Nucleus: -Megakaryocytes are characterized by having multiple nuclei, ranging from a few to several dozen. -The nuclei are often lobulated and located at the periphery of the cell, giving it a distinctive appearance. 3. Mitotic Ability: -Mature megakaryocytes, also known as polyploid megakaryocytes, undergo endomitosis, a process where the cell replicates its DNA without subsequent cell division. -This results in a cell with multiple sets of chromosomes and contributes to the formation of a large, multinucleated cell. 4. Nucleoli: -Megakaryocytes may have multiple nucleoli associated with each nucleus. -Nucleoli are involved in ribosomal RNA synthesis, indicating the cell's high metabolic activity. 5. Cytoplasm: -Megakaryocytes may have multiple nucleoli associated with each nucleus. -Nucleoli are involved in ribosomal RNA synthesis, indicating the cell's high metabolic activity. -The cytoplasm of megakaryocytes is abundant Megakaryocytes are located next to sinusoids, into which they protrude their cytoplasmic processes. These cytoplasmic processes fragment along complex, narrow invaginations of the plasmalemma, known as demarcation channels, into clusters of proplatelets. Shortly B-thrombopoiesis

30. 30 2-Megakaryocyte 1.Size and Shape: -Megakaryocytes are among the largest cells in the bone marrow, with a diameter ranging from 30 to 100 micrometers. -They are typically multi-lobulated and have a distinctive irregular shape. 2. Nucleus: -Megakaryocytes are characterized by having multiple nuclei, ranging from a few to several dozen. -The nuclei are often lobulated and located at the periphery of the cell, giving it a distinctive appearance. 3. Mitotic Ability: -Mature megakaryocytes, also known as polyploid megakaryocytes, undergo endomitosis, a process where the cell replicates its DNA without subsequent cell division. -This results in a cell with multiple sets of chromosomes and contributes to the formation of a large, multinucleated cell. 4. Nucleoli: -Megakaryocytes may have multiple nucleoli associated with each nucleus. -Nucleoli are involved in ribosomal RNA synthesis, indicating the cell's high metabolic activity. 5. Cytoplasm: -Megakaryocytes may have multiple nucleoli associated with each nucleus. -Nucleoli are involved in ribosomal RNA synthesis, indicating the cell's high metabolic activity. -The cytoplasm of megakaryocytes is abundant Megakaryocytes are located next to sinusoids, into which they protrude their cytoplasmic processes. These cytoplasmic processes fragment along complex, narrow invaginations of the plasmalemma, known as demarcation channels, into clusters of proplatelets. B-thrombopoiesis Electron micrograph of a megakaryocyte displaying segmentation in the formation of platelets. Although this cell possesses a single nucleus, it is lobulated, which gives the appearance of the cell possessing several nuclei ( × 3166).

31. 31 2-Megakaryocyte B-thrombopoiesis

32. 32 2-Megakaryocyte B-thrombopoiesis Photomicrograph of bone marrow section stained with H&E shows active hemopoietic centers in a close proximity to bone marrow sinusoids.

33. 33 3-Proplatlets 1.Size and Shape: -Proplatelets are elongated, filamentous structures resembling a beaded necklace, with swellings along their length that will eventually give rise to individual platelets. -They vary in size but are typically much smaller than the parent megakaryocyte. -As megakaryocytes extend proplatelets into the bloodstream, platelets are released from the tips of these extensions. -Various factors, including shear forces in the bloodstream and interactions with endothelial cells, contribute to the regulation of proplatelet formation and platelet release. 2. Nucleus: -Proplatelets are formed by the cytoplasmic extensions of mature megakaryocytes, and they lack a distinct nucleus themselves. 3. Mitotic Ability: -Proplatelets are not capable of mitosis as they represent a specialized stage in the differentiation of megakaryocytes. 4. Cytoplasm: -The cytoplasm of proplatelets contains the cellular components necessary for platelet function, including granules and other organelles. -The unique beaded structure along the proplatelets allows for the distribution of these components in a controlled manner. -Under electron microscopy, proplatelets reveal their filamentous structure, often resembling a string of beads. -Granules and other cytoplasmic components are visible along the length of the proplatelets, and the ends exhibit a bulbous structure where platelets will eventually be released. The megakaryocyte cytoplasm is converted into a mass of proplatelets, which are released from the cell. The nucleus is eventually extruded from the mass of proplatelets, and individual platelets are released from proplatelet ends. https://www.jci.org/articles/view/26891 https://www.science.org/doi/10.1126/science.1148946 B-thrombopoiesis

34. 34 3-Proplatlets Representative images of in situ bone marrow proplatelets; several elongated proplatelets (arrows) observed in a sinusoid vessel by scanning electron microscopy (SEM). Inset, magnification showing a bulbous proplatelets end. Note the various proplatelets shaft widths. https://www.haematologica.org/article/view/9731 B-thrombopoiesis

35. 35 Overview of proplatelet formation.  The assembly of platelets from megakaryocytes involves an elaborate dance that converts the cytoplasm into 100- to 500-μm-long branched proplatelets on which the individual platelets develop. The proplatelet and platelet formation process generally commences from a single site on the megakaryocyte where 1 or more broad pseudopodia form. Over a period of 4–10 hours, the pseudopodial processes continue to elongate and become tapered into proplatelets with an average diameter of 2–4 μm . Proplatelets are randomly decorated with multiple bulges or swellings, each similar in size to a platelet, which gives them the appearance of beads connected by thin cytoplasmic strings ( look at the opposite figure ). The generation of additional proplatelets continues at or near the original site of proplatelet formation and spreads in a wavelike fashion throughout the remainder of the cell until the megakaryocyte cytoplasm is entirely transformed into an extensive and complex network of interconnected proplatelets. The multilobed nucleus of the megakaryocyte cell body is compressed into a central mass with little cytoplasm and is eventually extruded and degraded. Platelet-sized swellings also develop at the proplatelet ends and are the primary sites of platelet assembly and release, as opposed to the swellings along the length of the proplatelet shaft (Figure  1 ). The precise events involved in platelet release from proplatelet ends have not been identified. Differential interference contrast image of proplatelets on a mouse megakaryocyte in vitro. Some of the hallmark features of proplatelets, including the tip, swellings, shafts, and a branch point, are indicated. Scale bar, 5 μm . 3-Proplatlets B-thrombopoiesis

36. 36 4-Platelets 1. Size and Shape: -Platelets are tiny, discoid cell fragments with an average diameter ranging from 2 to 3 micrometers. -They possess a flattened, discoid shape, allowing them to navigate through blood vessels. 2. Nucleus: -Platelets do not have a nucleus. The absence of a nucleus allows for increased flexibility and better functionality in their role during blood clotting. 3. Mitotic Ability: -Platelets are incapable of mitosis or cell division. They are derived from mature megakaryocytes through a unique process of cytoplasmic fragmentation. 4. Cytoplasm: -The cytoplasm of platelets contains various organelles, including dense granules and alpha-granules, which store bioactive molecules and proteins involved in blood clotting. -Under electron microscopy, platelets reveal a granular cytoplasm, with a distinctive open canalicular system that aids in the exchange of substances with the surrounding plasma. B-thrombopoiesis

37. Postnatal hemopoiesis C-Granulopoiesis

38. 38 C-Granulopoiesis Granulocytopoiesis , the formation of the granulocytes neutrophils, eosinophils, and basophils, and mast cells is under the influence of several cytokines, including stem cell factor, G-CSF and GM-CSF, PU.1 transcription factor, as well as IL-3, IL-5, IL-6, IL-8, and TNF- α . C-Granulopoiesis -if IL-5 is present, it drives the differentiation toward the formation of eosinophils. In the absence of IL-5, basophils form. - Mast cells also arise from myeloblasts but require stem cell factor for their differentiation

39. 39 1- Myeloblast The myeloblast is the earliest microscopically recognizable precursor cell in the bone marrow. 1.Size and Shape: -Myeloblasts are typically ranging in size from 12 to 14 micrometers in diameter. -They exhibit a round or oval shape with a high nuclear-to-cytoplasmic ratio. 2. Nucleus: -Myeloblasts have a single, large, round nucleus with fine chromatin. -The nucleus is centrally located within the cell. 3. Mitotic Ability: -Myeloblasts are highly mitotic and actively undergo cell division. 4. Nucleoli: - Myeloblasts may have three to five prominent nucleoli within the nucleus. -Nucleoli are involved in ribosomal RNA synthesis, reflecting the cell's high metabolic activity. 5. Cytoplasm: - The small amount of agranular cytoplasm stains intensely basophilic. - It contains Developing organelles, including rough endoplasmic reticulum ( rER ) and Golgi apparatus, are present in the cytoplasm, indicative of the cell's active protein synthesis. - A Golgi area is often seen where the cytoplasm is unstained. -no granules are present C-Granulopoiesis

40. 40 2- Promyelocyte 1.Size and Shape: -Promyelocytes are moderately-sized cells, typically ranging from 14 to 18 micrometers in diameter. -They exhibit a round or oval shape with a nucleus that is still relatively large. 2. Nucleus: -Promyelocytes have a large, round nucleus with fine chromatin. -The nucleus may contain one or more nucleoli, indicative of the cell's active metabolic state. 3. Mitotic Ability: -Promyelocytes maintain some mitotic activity, allowing for further proliferation and differentiation into more mature granulocytic cells. -This stage represents a transitional phase in which the cell is preparing for specialization. 4. Nucleoli: -Promyelocytes may have one or more nucleoli within the nucleus. -Nucleoli are involved in ribosomal RNA synthesis, supporting the cell's protein synthesis machinery. 5. Cytoplasm: -The cytoplasm of promyelocytes is less basophilic compared to earlier stage -Promyelocytes exhibit the formation of primary or azurophilic granules , which are the initial granules in the development of granulocytes. - Promyelocytes do not exhibit subtypes. Recognition of the neutrophil, eosinophil, and basophil lines is possible only in the next stage . C-Granulopoiesis

41. 41 3- Myelocyte 1.Size and Shape: Myelocytes are typically ranging from 10 to 12 micrometers in diameter. They exhibit a round or slightly indented shape. 2. Nucleus: -Myelocytes have a rounded or slightly indented nucleus. It acquires a distinct indentation during subsequent divisions. -The nucleus is still present in the cell but begins to show signs of condensation. 3. Mitotic Ability: -Myelocytes have reduced mitotic activity compared to earlier precursor cells. -The decrease in mitotic activity signifies a transitional phase toward further specialization. 4. Nucleoli: -Myelocytes generally lack nucleoli 5. Cytoplasm: -Specific granules in the cytoplasm become more apparent, indicating the cell's commitment to a specific granulocytic lineage. C-Granulopoiesis

42. 42 4- Metamyelocyte 1.Size and Shape: - Metayelocytes are typically ranging from 10 to 12 micrometers in diameter. 2. Nucleus: - They exhibit an indented or kidney-shaped nucleus, distinguishing them from earlier stages, with ongoing nuclear condensation. 3. Mitotic Ability: -Metamyelocytes have no mitotic ability. They represent a post-mitotic stage in granulocyte development. The reduction in mitotic activity indicates the commitment to the final stages of differentiation. 4. Nucleoli: -Metamyelocytes generally lack nucleoli, indicating a further reduction in ribosomal RNA synthesis activity compared to earlier stages. 5. Cytoplasm: - A few hundred granules are present in the cytoplasm of each metamyelocyte, and the specific granules of each variety outnumber the azurophilic granules. - Organelle population is reduced theoretically, the metamyelocyte stage in granulopoiesis is followed by the band stage and then the segmented stage. Although these stages are obvious in the neutrophil line, they are rarely, if ever, observed in the eosinophil and basophil lines in which the next easily recognized stages of development are the mature eosinophil and mature basophil , respectively. C-Granulopoiesis

43. 43 5- Band (stab) cell Band cells, also known as stab cells, are a stage in the maturation of granulocytes, specifically neutrophils. Here are key characteristics associated with band/stab cells: 1.Size and Shape: - Band cells are typically ranging from 9 to 12 micrometers in diameter. 2. Nucleus: - They are characterized by a distinctive elongated and of nearly uniform width ; thus giving them horseshoe or band-like appearance., which sets them apart from earlier stages in granulopoiesis. - It may exhibit condensation, indicating ongoing nuclear maturation. -in further maturation; Nuclear constrictions then develop to show nuclear lobulation 3. Mitotic Ability: - Band/stab cells are post-mitotic, meaning they have limited or no mitotic ability. -They represent a stage of granulocyte maturation that has progressed beyond the mitotic phases. 4. Nucleoli: -Band/stab cells generally lack nucleoli, indicating a further reduction in the cell's metabolic and synthetic activities compared to earlier stages. 5. Cytoplasm: - Band/stab cells contain specific granules that are more developed compared to earlier stages. -These granules contain enzymes and proteins involved in the immune response and antimicrobial activities. - Organelle population is reduced Although the percentage of band cells in the circulation is almost always low (0% to 3%), it may increase in acute or chronic inflammation and infection. . C-Granulopoiesis

44. 44 6- Mature cells C-Granulopoiesis Electron micrograph of a human mature neutrophil. The nucleus shows the typical multilobed confi guration with the heterochromatin at the periphery and the euchromatin more centrally located. A small Golgi apparatus ( G ) is present; other organelles are sparse. The punctate appearance of the cytoplasm adjacent to the convex aspect of the nuclear profi le is caused by glycogen particles. Adjacent to the concave aspect of the nuclear profi le are numerous granules. Specifi c granules appear less dense and more rounded than azurophilic granules. The latter are fewer in number and are extremely electron dense. Electron micrograph of a human eosinophil. The nucleus is bilobed, but the connecting segment is not within the plane of section. The granules are of moderate size, compared with those of the basophil, and show a crystalline body ( Cr ) within the less electron-dense matrix of the granule. M , mitochondria Electron micrograph of a human basophil. The nucleus appears as three separate bodies; the connecting strands are not in the plane of section. The basophil granules ( B ) are very large and irregularly shaped. Some granules reveal myelin fi gures ( MF ). M , mitochondria.

45. 45 Newly formed neutrophils leave the hemopoietic cords by piercing the endothelial cells lining the sinusoids rather than by migrating between them. C-Granulopoiesis

46. 46 C-Granulopoiesis

47. Postnatal hemopoiesis D-Monopoiesis

48. 48 D-Monopoiesis D-monopoiesis

49. 49 1-Monoblast Monoblasts are precursor cells in the process of monocytopoiesis , representing an early stage in the development of monocytes. Here are key characteristics associated with monoblasts : 1.Size and Shape: - Monoblasts are relatively large cells with a diameter ranging from 14 to 20 micrometers. -They typically exhibit a round or oval shape. 2. Nucleus: - Monoblasts have a single, large, and centrally located nucleus. -The nucleus is typically round or oval in shape and contains fine chromatin. 3. Mitotic Ability: - Monoblasts possess the ability to undergo mitosis, allowing for cell division and the generation of additional precursor cells in the monocyte lineage. 4. Nucleoli: - Monoblasts may have one or more prominent nucleoli within the nucleus. -Nucleoli are involved in ribosomal RNA synthesis, indicating the cell's high metabolic activity. 5. Cytoplasm: -The cytoplasm of monoblasts is abundant and basophilic, meaning it stains blue-purple with basic dyes. -It contains developing organelles, including rough endoplasmic reticulum ( rER ) and Golgi apparatus, indicative of the active protein synthesis characteristic of precursor cells. D-monopoiesis monoblasts in blood film are observed in monoblastic and myelomonocytic leukemias.

50. 50 2-Promonocyte Promonocytes are intermediate cells in the process of monocytopoiesis , representing a stage between monoblasts and mature monocytes. The transformation of MoPs to monocytes takes about 55 hours, Here are key characteristics associated with promonocytes: 1.Size and Shape: -Promonocytes are similar to the monoblast , with a diameter ranging from 14 to 20 micrometers. -They exhibit a round or slightly indented shape. 2. Nucleus: -Promonocytes typically have a single, large, and eccentrically located nucleus. -The nucleus may exhibit irregular contours (indented) and a finer chromatin pattern compared to earlier precursor cells 3. Mitotic Ability: -Promonocytes retain the ability to undergo mitosis, allowing for further proliferation and differentiation into mature monocytes. -The mitotic activity contributes to the expansion of the monocyte population. 4. Nucleoli: -The nucleus of promonocytes may contain one or more nucleoli, although they are generally less prominent than in earlier precursor cells. -Nucleoli are involved in ribosomal RNA synthesis, indicating the cell's ongoing metabolic activity. 5. Cytoplasm: -The cytoplasm of promonocytes is abundant and exhibits a slight basophilia. -Developing organelles, including rough endoplasmic reticulum ( rER ) and Golgi apparatus, are present in the cytoplasm, supporting the cell's protein synthesis activities. D-monopoiesis

51. 51 3-Monocyte Monocytes representing the final stage of differentiation in the monocytopoiesis process. Here are key characteristics associated with monocytes: 1.Size and Shape: -Monocytes are relatively large cells with a diameter ranging from 12 to 20 micrometers. 2. Nucleus: - Monocytes have a single, large, and kidney-shaped nucleus that may exhibit a folded or lobulated appearance. -The nucleus is often eccentrically located within the cell. 3. Mitotic Ability: -Fully mature monocytes have limited mitotic ability. They typically circulate in the bloodstream in a non-dividing state. -In response to certain stimuli, monocytes can migrate to tissues where they may undergo further differentiation into m acrophages, monocyte-derived dendritic cells, osteoclasts and microglia. 4. Nucleoli: -Monocytes generally have a non-prominent nucleolus within the nucleus. 5. Cytoplasm: -The cytoplasm of monocytes is abundant and typically agranular and contains various organelles such as lysosomes (azurophilic granules) and endoplasmic reticulum. -The cytoplasm may also display vacuoles, reflecting the cell's phagocytic activity and ability to engulf foreign particles . D-monopoiesis

52. 52 D-monopoiesis 3-Monocyte

53. Postnatal hemopoiesis E- lymphpoiesis

54. 54 E-lymphopoiesis E-lymphopoiesis 1. Hematopoietic Stem Cells (HPSCs): 2. Common Lymphoid Progenitor (CLP) or (CFU-Ly): The differentiation of CFU-Ly to CFU- LyB and CFU- LyT requires he expression of zinc finger proteins, namely the Ikaros family of transcription factors as well as the expression of a moderate level of PU.1 transcription factor. 3. B and T Cell Commitment and Maturation: B-cells: CFU- LyB in bone marrow divides several times, giving rise to immunocompetent B lymphocytes expressing specific surface markers, including antibodies. - B cells undergo rearrangement of their immunoglobulin genes, leading to the expression of unique B cell receptors (BCRs). Mature B cells with functional BCRs are released into the bloodstream. T-cells: CFU- LyT cells undergo mitosis, forming immunoincompetent T cells, which travel to the cortex of the thymus, where they proliferate, mature, and begin to express cell surface markers. As these surface markers appear on the T-cell plasmalemma the cells become immunocompetent T lymphocytes. Most of these newly formed T cells are destroyed in the thymus and are phagocytosed by resident macrophages. The process of T cell maturation is partially controlled by IL-7 and GATA3 transcription factor. NKC: NK cells also migrate to a yet unknown region of the bone marrow where they will become immunocompetent. The process of NK cell maturation is partially controlled by IL-12 and IL-15. Migration and Circulation: - Mature lymphocytes, including T cells, B cells, and NK cells, leave their sites of maturation (thymus for T cells, bone marrow for B cells and NK cells) and enter the bloodstream. - They circulate throughout the body, patrolling lymphoid tissues and organs.

55. 55 E-lymphopoiesis E-lymphopoiesis

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57. Thank you 57