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Haematopoiesis

Haematopoiesis. Haematopoiesis. This is the development of all blood cells from multipotent stem cells, termed haematopoietic stem cell (HSC), characterised by CD34, which in adults occurs in the bone marrow. Haematopoietic stem cell. Stem cells have two essential properties self renewal

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Haematopoiesis

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  1. Haematopoiesis

  2. Haematopoiesis • This is the development of all blood cells from multipotentstem cells, termed haematopoietic stem cell (HSC), characterised by CD34, which in adults occurs in the bone marrow.

  3. Haematopoietic stem cell • Stem cells have two essential properties • self renewal • potency. • Self renewal of course means that they can proliferate, indefinitely in the case of some. • Potency means thay can generate a range (one or many) differentiated cell types. • Stem cells themselves are undifferentiated i.e. have no specific functions other than division.

  4. Haematopoietic stem cell • Stem cells occupy a special niche in tissues which may help to define their “stem-ness”. • At division, one cell leaves the niche and becomes a transit cell, the other stays put • asymmetric division in space as well as in kind niche containing stem cell and transit cell outside niche niche containing stem cell niche containing dividing stem cell

  5. Haematopoietic stem cell • The niche is a complex organisation of stromal (i.e. non-haematopoietic cells) interacting via adhesion molecules with the stem cell. • There may be more than one kind of niche in a tissue. Li, Z. & Li, L. (2008) Understanding hematopoietic stem-cell microenvironments. Trends in Biochemical Sciences 31:589-505

  6. Haematopoietic stem cell • The role of the transit cell is to divide rapidly but a limited number of times so amplifying cell numbers • and its progeny differentiate to form the functional end cell of that particular lineage.

  7. Haematopoietic stem cell long-lived stem cell in special niche slowly cycles: one daughter is a new stem cell, the other is a transit cell which leaves the niche the transit cell amplifies the cell number, going through a limited number of divisions the amplified cells finally form functional end cells, which do not divide.

  8. Haematopoiesis • In haematopoiesis there is an intervening step called a “progenitor cell” • this is like a stem cell in that it is multipotent (tho’ less so than the HSC) • it is unlike the stem cell in that it does not divide indefinitely • (a controversial issue).

  9. Haematopoiesis • There are 2 progenitor cells in haematopoiesis: • Common lymphoid progenitors (CLPs) which give rise to all lymphoid cells. • Common myeloid progenitors (CMPs) which give rise to all other blood cells including erythrocytes and platelets.

  10. The haematopoietic stem cell CLP Lymphocytes HSC Granulocytes erythrocytes thrombocytes CMP Progenitor cells, dividing and committed Transit cells, dividing and differentiating End cells, not dividing, functional

  11. Haematopoiesis • B cells & LGLs mature from CLPs in the bone marrow. • Early T cell precursors derived from CLPs migrate to the thymus where they complete their maturation and then enter the periphery as CD4 or CD8 cells. • A key step in the differentiation of B & T lymphocytes is development of their antigen receptors sIg and TCR.

  12. Haematopoiesis • CMPs give rise to either • megakaryocyte (generates platelets)/erythrocyte or • granulocyte/macrophage progenitors. • These latter differentiate within the bone marrow to give rise to all the myeloid cells.

  13. Haematopoiesis What drives haematopoiesis? • A range of proteins which drive growth and differentiation which bind to specific receptors on the developing cells. • These are generated • by the stromal cells of the primary lymphoid tissues, & may be cell-surface expressed (juxtacrine); • or (especially during infection/inflammation) by activated leukocytes in other tissues (paracrine).

  14. Simplified haematopoiesis schema pre-T CLP pre-B pre-G,M thymus CD4-,CD8- DN Bone marrow periphery CD4 T cell CD8 T cell B cell CD34 stem cell monocytes granulocytes CMP pre-E,Meg erythrocytes platelets see notes, next slide

  15. Simplified haematopoiesis schema • MANY INTERMEDIATE STEPS OMITTED. • GROWTH FACTORS OMITTED. • Dendritic cells omitted • probably arise from both both CLP & CMP. • LGL/NK cells omitted - parallel B cells. • Periphery = circulation and all tissues except 1ry lymphoid. • Communication between compartments via circulation. • Meg = megakaryocyte; DN = double negative.

  16. Haematopoiesis • The process of haematopoeisis is obviously much more complex than presented here. • Go to Haematopoiesis - less simple version for a much fuller account of haematopoiesis.

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