Hematopoiesis

• Hemopoiesis


  Blood cell formation
• Stem cells


  • Pluripotent cells capable of asymmetric division and self-renewal
  • Some daughter cells form specific, irreversibly committed progenitor cells
  • Other daughter cells remain as a small pool of slowly dividing stem cells
• Identifying hemopoietic stem cells

  1. Use fluorescence-labeled antibodies to mark specific cell surface antigens

  2. Pass cell population through a fluorescence-activated cell-sorting (FACS) instrument
• In vivo techniques to study hemopoiesis

  1. Inject bone marrow of normal donor mice into irradiated mice whose hematopoietic cells have been destroyed

  2. Transplanted bone marrow cells produce hematopoietic colonies in the bone marrow and spleen
• In vitro techniques to study hemopoiesis

  1. Use semisolid tissue culture media containing substances produced by marrow stromal cells

  2. Identify and study cytokines promoting hemopoietic cell growth and differentiation
• Hemopoietic stem cell


  Single type of pluripotent cell in the bone marrow that can give rise to all the blood cell types
• Major lineages of progenitor cells

  • Lymphoid cells (lymphocytes)
  • Myeloid cells (granulocytes, monocytes, erythrocytes, megakaryocytes)
• Hemopoietic growth factors (colony-stimulating factors, cytokines)

  Glycoproteins that stimulate proliferation of progenitor and precursor cells and promote cell differentiation and maturation within specific lineages
• Major hemopoietic cytokines

  • Stem cell factor (SCF)
  • Erythropoietin (EPO)
  • Thrombopoietin (TPO)
  • Granulocyte-macrophage colony-stimulating factor (GM-CSF)
  • Granulocyte colony-stimulating factor (G-CSF or filgrastim)
  • Monocyte colony-stimulating factor (M-CSF)
  • Interleukin-1 (IL-1)
  • Interleukin-2 (IL-2)
  • Interleukin-3 (IL-3)
  • Interleukin-4 (IL-4)
  • Interleukin-5 (IL-5) or eosinophil differentiation factor (EDF)
  • Interleukin-6 (IL-6)
  • Interleukin-7 (IL-7)
• Progenitor cells (colony-forming units, CFUs)

  Give rise to colonies of only one cell type when cultured in vitro or injected into a spleen
• Major types of progenitor cells/CFUs

  • Erythroid lineage of erythrocytes
  • Thrombocytic lineage of megakaryocytes for platelet formation
  • Granulocyte-monocyte lineage of all three granulocytes and monocytes
  • Lymphoid lineage of B lymphocytes, T lymphocytes, and natural killer cells
• Precursor cells (blasts)

  Gradually assume the morphologic characteristics of the mature, functional cell types they will become
• Stem and progenitor cells cannot be morphologically distinguished and simply resemble large lymphocytes</b>
• Progenitor and precursor cells divide more rapidly, producing large numbers of differentiated, mature cells
• Hemopoietic microenvironment (niche)

  Specific endocrine, paracrine, and juxtacrine factors provided largely by the local cells and extracellular matrix (ECM) of the hemopoietic organs
• Bone marrow

  • Found in the medullary canals of long bones and in the small cavities of cancellous bone
  • Two types: blood-forming red bone marrow and yellow bone marrow filled with adipocytes
• In the newborn all bone marrow is red and active in blood cell production, but as the child grows, most of the marrow changes gradually to the yellow variety
• Red bone marrow

  • Contains a reticular connective tissue stroma, hemopoietic cords or islands of cells, and sinusoidal capillaries
  • Stroma is a meshwork of specialized fibroblastic cells called stromal cells and a delicate web of reticular fibers supporting the hemopoietic cells and macrophages
  • Matrix contains collagen type I, proteoglycans, fibronectin, and laminin
• Red marrow is also a site where older, defective erythrocytes undergo phagocytosis by macrophages, which then reprocess heme-bound iron for delivery to the differentiating erythrocytes
• Erythropoiesis

  Origin and maturation of erythrocytes
• Granulopoiesis

  Origin and maturation of granulocytes
• Monocytopoiesis

  Origin and maturation of monocytes
• Thrombocytopoiesis


  Origin and maturation of platelets
• Lymphopoiesis


  Lymphocyte development in the marrow and lymphoid organs
• T and B cells

  Promotes T helper cells