HISTOPATHOLOGY: STEM CELL AND ORGANIZERS

Course: Histopathology
Topic: stem cell, types and organizers

1. STEM CELLS, PATTERN FORMATION AND HOMEOBOX GENES LECTURE NOTES BY CHRIS MBA

2. Stem cells are undifferentiated mass of cells that has the ability to continuously divide and differentiate (develop) into various other kind(s) of cells/tissues. The human body has a variety of 220 different cells types. Stem cells are master cells that act as foundation cells for every organ, tissue and cell in the body.. They are considered as a blank microchip that can be programmed to perform particular tasks. They serve as a repair machine for the body. 5/18/2020 EMBRYOLOGICAL MECHANISM 2 WHAT ARE STEM CELLS?

3. ‘Blank cells’ (unspecialized) Capable of dividing and renewing themselves for long periods of time (proliferation and renewal) Have the potential to give rise to specialized cell types (differentiation) 5/18/2020 EMBRYOLOGICAL MECHANISM 3 CHARACTERISTICS OF STEM CELLS

4. Stem cells can be classified into four broad categories, based on their ability to differentiate Totipotent stem cells are found only in early embryos. Each cell can form a complete organism (1-3 days) . Pluripotent stem cells exist in the undifferentiated inner cell mass of the blastocyst (5 to 14 days) and can form any of the over 200 different cell types found in the body. stem cells can form most or all cell types in the adult 5/18/2020 EMBRYOLOGICAL MECHANISM 4 CLASSIFICATION OF STEM CELLS

5. Multipotent stem cells are derived from fetal tissue, cord blood, and adult stem cells. These cells are differentiated, but can form a number of other tissues. stem cells can form multiple types of cells and tissue types Unipotent : able to contribute to only one mature cell type but have the property of self-renewal which distinguishes 5/18/2020 EMBRYOLOGICAL MECHANISM 5 CLASSIFICATION OF STEM CELLS

6. Pluripotent Stem Cells – more potential to become any type of cell 5/18/2020 EMBRYOLOGICAL MECHANISM 6 PLURIPOTENT STEM CELL

7. Multipotent stem cells – limited in what the cells can become 5/18/2020 EMBRYOLOGICAL MECHANISM 7 MULTIPOTENT STEM CELL

8. Embryonic stem cells Embryonic germ cells Adult stem cells Totipotent Pluripotent Multipotent Unipotent 5/18/2020 EMBRYOLOGICAL MECHANISM 8 FURTHER CLASSIFICATION OF STEM CELLS

9. Induction - is the stimulation of a cell to differentiate in response to a stimulus produced by another cell. It is mediated by inducer substances that diffuse from one cell to another. It results in cell determination. Determination is the commitment of a cell to undergo differentiation. It is an irreversible process but is not accompanied by morphological changes. 5/18/2020 EMBRYOLOGICAL MECHANISM 9 DEFINITION OF TERMS

10. Determinants are the cytoplasmic effector molecules that mediate determination. Differentiation is the variation in the pattern of expression of a common set of genes to form cells of diverse morphology and function. 5/18/2020 EMBRYOLOGICAL MECHANISM 10

11. Cells found early (less than 2 wks.) in the development of an embryo Embryonic stem(ES) cells are the most versatile because they can become any cell in the body including fetal stem cells and adult stem cells . Embryonic stem (ES) cells are taken from inside the blastocyst , a very early stage embryo. ES cells are found in the inner cell mass . 5/18/2020 EMBRYOLOGICAL MECHANISM 11 EMBRYONIC STEM (ES) CELLS

12. 5/18/2020 EMBRYOLOGICAL MECHANISM 12 The blastocyst is a ball of about 50-100 cells and is made up of an outer layer of cells, a fluid-filled space and a group of cells called the inner cell mass .

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14. 5/18/2020 EMBRYOLOGICAL MECHANISM 14 ADVANTAGE: NO NEED FOR EMBRYOS!

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16. Human embryonic germ cells (EG cells) normally develop into eggs and sperm . They are derived from a specific part of the embryo called the gonad ridge , and are isolated from fetuses older than 8 weeks of development. One advantage of embryonic germ cells is that they do not appear to generate tumors when transferred into the body, as embryonic stem cells do. EG cells are isolated from terminated pregnancies and no embryos or foetuses are created for research purposes. 5/18/2020 EMBRYOLOGICAL MECHANISM 16 Embryonic germ cells

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18. Adult stem cells are found in the human body and in umbilical cord blood. The most well known source of adult stem cells in the body is bone marrow but they are also found in many organs and tissues; even in the blood . Adult stem cells are more specialized since they are assigned to a specific cell family such as blood cells,nerve cells , etc. Recently, it was discovered that an adult stem cell from one tissue may act as a stem cell for another tissue, i.e. blood to neural 5/18/2020 EMBRYOLOGICAL MECHANISM 18 ADULT STEM CELLS

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21. Hematopoietic stem cells are those cells from where all blood cells originate. Pluripotent :- red cells, white cells and platelets. Sources of hematopoietic stem cells in human : - 1.Umbilical Cord blood. 2.Peripheral blood. 3.Bone marrow 5/18/2020 EMBRYOLOGICAL MECHANISM 21 HEMATOPOIETIC STEM CELLS

22. Positional information  is a theory of how cells acquire  positional  identity and value related to their  position  along a line with respect to boundaries at both ends of the line. Positional information  is a concept that relates to  pattern formation , that is, the development of spatial organization  in the  embryo that results from cells differentiating at specific positions. ... 5/18/2020 EMBRYOLOGICAL MECHANISM 22 Positional information

23. This is the basis of  positional information  which requires that the cells have  positional  values as  in a  coordinate system. Positional information  has been suggested  to  play a central role  in  pattern formation  during development . 5/18/2020 EMBRYOLOGICAL MECHANISM 23

24. Pattern formation refers to the generation of complex organizations of cell fates in space and time. During embryogenesis, information encoded in the genome is translated into cell proliferation, morphogenesis, and early stages of differentiation 5/18/2020 EMBRYOLOGICAL MECHANISM 24 PATTERN FORMATION

25. In developmental biology, pattern formation describes the mechanism by which initially equivalent cells in a developing tissue in an embryo assume complex forms and functions (Ball, 2009) The process of embryogenesis involves coordinated cell fate control (Lai, 2004; Tyler and Cameron, 2007). 5/18/2020 EMBRYOLOGICAL MECHANISM 25 INTRODUCTION TO PATTERN FORMATION

26. Pattern formation is genetically controlled, and often involves each cell in a field sensing and responding to its position along a morphogen gradient. This is followed by short distance cell-to-cell communication through cell signaling pathways to refine the initial pattern. 5/18/2020 EMBRYOLOGICAL MECHANISM 26

27. The reliable development of highly complex organisms is an intriguing and fascinating problem. The genetic material is, as a rule, the same in each cell of an organism. How then do cells, under the influence of their common genes, produce spatial patterns ? Development of an organism is, of course, under genetic control but the genetic information is usually the same in all cells. A crucial problem is therefore the generation of spatial patterns that allow a different fate of some cells in relation to others. 5/18/2020 EMBRYOLOGICAL MECHANISM 27 Why Pattern Formation?

28. Every organism has a unique body pattern. This patterning is controlled and influenced by the HOMEOBOX genes . These genes specify how different areas of the body develop their individual structures, e.g. Arms, legs etc. 5/18/2020 EMBRYOLOGICAL MECHANISM 28 GENES OF PATTERN FORMATION

29. Homeotic genes are regulatory genes that determine where certain anatomical structures, such as appendages, will develop in an organism during morphogenesis. Homeobox genes are a large group of similar genes that direct the formation of many body structures during early embryonic development 5/18/2020 EMBRYOLOGICAL MECHANISM 29 WHAT ARE HOMEOBOX GENES?

30. The expression of homeotic genes results in the production of a protein ( homeodomain ) that can turn on or switch off other genes . These genes act as Transcription factors. Homeobox genes are present on every human chromosome, and they often appear in clusters 5/18/2020 EMBRYOLOGICAL MECHANISM 30

31. Genes in the homeobox group are involved in a wide range of critical activities during development. These activities include directing the formation of limbs and organs along the anterior-posterior axis (the imaginary line that runs from head to tail in animals) and regulating the process by which cells mature to carry out specific functions (differentiation). Some homeobox genes act as tumor suppressors, which means they help prevent cells from growing and dividing too rapidly or in an uncontrolled way. 5/18/2020 EMBRYOLOGICAL MECHANISM 31

32. Morphogens are signaling molecules that emanate from a restricted region of a tissue and spread away from their source to form a concentration gradient. As the fate of each cell in the field depends on the concentration of the morphogen signal, the gradient prefigures the pattern of development 5/18/2020 EMBRYOLOGICAL MECHANISM 32 Morphogens