Cellular Dynamics of Hematopoiesis

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Cellular Dynamics of Hematopoiesis

• Lecture C4-02
• October 23, 2002
• Robert Chervenak, Ph.D.

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Stem Cells
Self Renewal
Differentiation
Stem Cell
Differentiated Cell
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Stem Cells
Active Regulation
Self Renewal
Differentiation
Stem Cell
Differentiated Cell
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Stem Cells
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Stem Cells
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Stem Cells
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Stem Cells
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Stem Cells
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Mechanisms of Regulation of Hematopoiesis

• Control of cytokine production by stromal cells
  (altering the microenvironment)
• Movement of developing cells to from one
  microenvironment to another
• Production of cytokines by non-stromal cells

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Stromal Cells Regulate Stem Cells
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Critical Cytokines in Hematopoiesis

• Interleukin 3 (IL-3)
• Produced by T cells (Th1 and Th2)
• Binds to IL-3 Receptors on progenitors
• Maintains stem cells and early progenitors
• Induces proliferation
• Does not appear to induce differentiation

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Critical Cytokines in Hematopoiesis

• Stem Cell Factor
• AKA Steel Factor, Mast Cell Growth Factor, c-kit
  ligand
• Produced by stromal cells
• Binds to c-kit on progenitors
• Maintains stem cells and early progenitors
• Induces proliferation
• Does not appear to induce differentiation

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Critical Cytokines in Hematopoiesis

• Factors important for late progenitors
• erythropoietin (EPO)
• needed for red blood cell development
• GM-CSF
• works on common granulocyte/monocyte precursor
• G-CSF
• works on granulocyte-committed progenitors
• M-CSF
• works on monocyte/macrophage progenitors

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Mechanisms of Regulation of Hematopoiesis

• Control of cytokine production by stromal cells
  (altering the microenvironment)
• Movement of developing cells to from one
  microenvironment to another
• Production of cytokines by non-stromal cells

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Mechanisms of Regulation of Hematopoiesis

• Control of cytokine production by stromal cells
  (altering the microenvironment)
• Movement of developing cells to from one
  microenvironment to another
• Production of cytokines by non-stromal cells

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Immune Response
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Mechanisms of Regulation of Hematopoiesis

• Up- or down-regulate cytokine receptor expression
  by developing cells
• Removal of developing (and developed) cells by
  apoptosis

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Growth Factor
Stromal Cell
Stem Cell
Response
Growth Factor Receptor
Stromal Cell
Stem Cell
No Response
Stromal Cell
Stem Cell
No Response
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Mechanisms of Regulation of Hematopoiesis

• Up- or down-regulate cytokine receptor expression
  by developing cells
• Removal of developing (and developed) cells by
  apoptosis

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Two Types of Cell Death
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Developmental Sites of Hematopoiesis
Neonate
Fetus
Adult
Yolk Sac
?
Fetal Liver
Spleen
Bone Marrow