7. hematopoiesis

Hematopoiesis

1. Presenter: Dr G Santhi priya Moderator: Dr Rajeev

2. Contents Introduction and development Hematopoiesis Cytokines and the Control of Hematopoiesis Cytokine Receptors, Signaling Pathways, and Transcription Factors Hematopoietic Microenvironment References

3. The pioneering work of Till and McCulloch began to define the hierarchy of hematopoietic precursor cells using in vivo clonal assays. H ematopoietic stem cells (HSCs) develop in discrete anatomical niches, migrating during embryogenesis from the aorta- gonadmesonephros (AGM) region to the fetal liver, and finally to the bone marrow, where most HSCs reside throughout adult life. 1. Introduction and development

4. 2. Hematopoiesis Defination : “ The processes involved in the production of all of the various cells of the blood from the HSCs are collectively called hematopoiesis ” Highly regulated process to maintain circulating cell numbers within relatively constant levels and to respond rapidly to conditions requiring extra cells . Ma i n t a i n s b a l a nc e be t ween sel f r ene w a l , ter m i n al differentiati o n , m i g r ation, a n d ce l l death.

5. Sites of hematopoiesis

6. Hematopoietic cells

7. Stem Cells Multipotential precursors Stem Cell Phenotype: CD34 + Thy-1 + CD49f + CD38 - Lin - HLADR - Rh123 Lo

8. The Stem Cell Compartment “age hierarchy” long-term repopulating cells (LTRs) short-term repopulating cells (STRs)

9. Stem Cell Niches Ligand signaling pathway Growth factor receptor interactions

10. Progenitor Cells Populations of differentiating cells that have an increasingly limited capacity to self-renew and are gradually more restricted in differentiation options. Lineage-specific transcription factors are thought to play essential roles in this process

11. 3 . Cytokines and the Control of Hematopoiesis Growth factors / Cytokines

12. 3. Cytokines and the Control of Hematopoiesis Growth factors / Cytokines Early-Acting ( Multilineage ) Growth Factors Stem Cell Factor (SCF) Flt3 Ligand (FL) Interleukin 3 GM-CSF Interleukin 6 Interleukin 11 Later-Acting (Lineage-Restricted) Growth G-CSF Factors M-CSF EPO Indirect-Acting Growth Factors TPO Other Stem Cell Regulators IL-5 IL-2,-4, -7, -10, -12, -13, -14, -15

13. 4. Cytokine Receptors, Signaling Pathways, and Transcription Factors Cytokine Receptors: homodimers / heterodimers or heterotrimers Receptors with Intrinsic Tyrosine Kinase Domains Hematopoietic Growth Factor Receptor Superfamily Receptor Functional Domains

14. Signaling Pathways

15. Transcription Factors TFs associated with the activation of a particular lineage-specific differentiation program often simultaneously inhibit alternate lineage-specific transcription factors. Interestingly, more than half of the hematopoietic transcription factors identified have been shown to be dysregulated in hematologic malignancies (translocations, point mutations of TF genes) Thus, the impaired differentiation seen in leukemia is likely due to abnormalities of critical, discrete pathways of transcriptional control.

16. Clinical Use of Hematopoietic Growth Factors

17. 5.Hematopoietic microenvironment

18. 5.Hematopoietic microenvironment

19. HSC niche players in the adult bone marrow

20. The aging HSC niche

21. McKenzie SB, Williams JL. Hematopoiesis.In : Clinical labouratory hematology, 3rd ed.Pearson;2016 p71-91 . Singh T. Normal hematopoiesis and evaluation of bone marrow and peripheral blood film. In: Atlas and Text of Haematology,3 rd ed.Delhi:2014.P.1-4 Diseases of white blood cells, lymph nodes,spleen and thymus. In Kumar V, Abbas A K, Aster J C, Robbins and cotran patholology basis of disease. 9 th ed. Elsevier Inc: 2016. P.579-82. References

22. Gao X, Xu C, Asada N, Frenette PS. The hematopoietic stem cell niche: from embryo to adult. Development 2018;145:1-12 Laffan M A, Manning R , Investigation of hemostasis , Bain B.J, Bates I, Laffan M.A, Lewis S.M, Dacie and Lewis Practical Haematology . 11 th ed. London: 2012. P.424-39 Mathur SC,Hutchison RE,Mahi G. Hematopoiesis .In Bain B.J, Bates I, Laffan M.A, Lewis S.M, Dacie and Lewis Practical Haematology . 11 th ed. London: 2012. P.540-58 References

23. Thank you!!!