Regulation of Hematopoiesis lecture 5!!!

Vocabulary flashcards covering key hematopoiesis concepts and growth factors from the lecture notes.

Hematopoiesis

Production of blood cells; governed by multiple cytokines.

Cytokines

Growth factors produced by many cell types that regulate hematopoiesis (survival, proliferation, differentiation) and act via receptors.

Differentiation

Appearance of different properties in cells that were initially equivalent, leading to specialization.

Commitment

The point at which two cells from the same precursor take separate developmental routes.

Maturation

Execution of commitment; progression toward a mature cell phenotype.

Hematopoietic Stem Cell (HSC)

Undifferentiated, multipotent cell that can give rise to all blood lineages; small, long-lived, often quiescent.

Self-renewal

HSCs’ ability to produce more stem cells that retain stem cell properties.

Quiescence

A non-dividing state; most HSCs are in quiescence.

CMP (Common Myeloid Progenitor)

Progenitor that gives rise to myeloid lineages.

CLP (Common Lymphoid Progenitor)

Progenitor that gives rise to lymphoid lineages.

MPP (Multipotent Progenitor)

Progenitor that is still multipotent but with limited self-renewal.

LMPP (Lymphoid-Primed Multipotent Progenitor)

Early progenitor with potential for lymphoid development.

GMP (Granulocyte-Monocyte Progenitor)

Progenitor giving rise to granulocytes and monocytes.

MEP (Megakaryocyte-Erythrocyte Progenitor)

Progenitor that gives rise to megakaryocytes and erythrocytes.

BFU-E

Burst-Forming Unit-Erythroid; early erythroid progenitor.

CFU-E

Colony-Forming Unit-Erythroid; erythroid progenitor primarily regulated by EPO.

BFU-Mk

Burst-Forming Unit-Megakaryocyte; early megakaryocyte progenitor.

CFU-Mk

Megakaryocyte Colony-Forming Unit; progenitor for megakaryocytes.

EPO (Erythropoietin)

Growth factor regulating erythropoiesis; mainly acts on CFU-E.

SCF (Stem Cell Factor / KIT Ligand)

Growth factor supporting HSC growth and survival via KIT receptor.

FL (Flt3 Ligand)

Growth factor involved in early hematopoiesis.

IL-3

Interleukin-3; supports multipotent progenitors.

IL-6

Interleukin-6; early-acting multilineage growth factor.

IL-11

Interleukin-11; influences megakaryopoiesis and other lineages.

GM-CSF

Granulocyte–Macrophage Colony-Stimulating Factor; promotes granulocyte and macrophage development.

G-CSF

Granulocyte Colony-Stimulating Factor; stimulates granulocyte production (neutrophils).

M-CSF

Macrophage Colony-Stimulating Factor; promotes monocyte/macrophage lineage.

TPO (Thrombopoietin)

Promotes megakaryocytopoiesis and platelet production.

Erythropoiesis

Production of erythrocytes; regulated by EPO; BFU-E and CFU-E stages.

Granulopoiesis

Production of granulocytes (neutrophils, eosinophils, basophils) from GMP via growth factors like G-CSF and GM-CSF.

Monopoiesis

Production of monocytes from monocyte lineage; influenced by M-CSF and GM-CSF.

Megakaryocytopoiesis

Development of megakaryocytes leading to platelets.

Thrombopoiesis

Platelet production from megakaryocytes; driven by TPO and associated cytokines.

Lymphopoiesis

Production of lymphocytes; occurs in bone marrow, thymus, lymph nodes, and spleen.

BLAST

First morphologically recognizable hematopoietic cell in maturation.

Pronormoblast / Erythroblast

Early erythroid precursor stage in erythropoiesis.

Normoblast (Orthochromic Normoblast)

Later erythroid precursor before reticulocyte formation.

Megakaryoblast

Megakaryocyte precursor cell in megakaryocytopoiesis.

Reticulocyte

Immature erythrocyte released into the bloodstream during erythropoiesis.

Negative Regulators

Factors that limit hematopoiesis (e.g., INF, TGF-β, TNF-α).

Interferons (INF)

Cytokines that can inhibit hematopoietic cell production.

Transforming Growth Factor-β (TGF-β)

Cytokine that can inhibit hematopoietic proliferation and differentiation.

TNF-α (Tumor Necrosis Factor-α)

Cytokine that can inhibit hematopoiesis and promote apoptosis in some contexts.

Paracrine signaling

Cytokine communication where signals act on nearby cells.

Juxtacrine signaling

Signaling requiring cell-to-cell contact in hematopoiesis.

Long-Term Repopulating (LTR)

Subset of HSCs capable of long-term hematopoietic reconstitution.

Short-Term Repopulating (STR)

Subset of HSCs replenishing more quickly but with limited longevity.

What is the typical lifespan of granulocytes?

Approximately 1 \text{ to } 2 days in circulation.

What is the typical lifespan of erythrocytes?

Approximately 120 days.

What is the typical lifespan of platelets?

Approximately 7 \text{ to } 10 days.

Compare the proliferation and differentiation potential of Hematopoietic Stem Cells (HSCs) with progenitor cells and maturing cells.

1. Hematopoietic Stem Cells (HSCs):
   • Low proliferation (often quiescent),
   • Undifferentiated, multipotent with self-renewal.
2. Progenitor Cells (e.g., CMP, CLP):
   • High proliferation,
   • Limited multipotency or committed to specific lineages, more differentiated than HSCs.
3. Maturing Cells (e.g., BLAST, Reticulocyte):
   • Actively dividing initially, progressively lose proliferative capacity,
   • Highly committed, undergoing terminal differentiation.

Compare the morphology and population size of Hematopoietic Stem Cells (HSCs) with progenitor cells and maturing cells.

1. Hematopoietic Stem Cells (HSCs):
   • Small, undifferentiated appearance,
   • Very rare population.
2. Progenitor Cells:
   • Vary in morphology, generally larger than HSCs and show some lineage commitment,
   • More numerous than HSCs.
3. Maturing Cells:
   • Distinct morphological changes leading to mature phenotype,
   • Most numerous cell population.

Describe the general hierarchy of hematopoietic precursor cells from most undifferentiated to lineage-committed progenitors.

Hematopoietic Stem Cell (HSC) \rightarrow Multipotent Progenitor (MPP) \rightarrow Common Myeloid Progenitor (CMP) / Common Lymphoid Progenitor (CLP) \rightarrow Lineage-specific Progenitors (e.g., GMP, MEP, BFU-E, CFU-E for myeloid; LMPP for lymphoid).

From which common progenitor do granulocytes, monocytes, megakaryocytes, and erythrocytes derive?

Granulocytes and monocytes derive from the Granulocyte-Monocyte Progenitor (GMP), which comes from the Common Myeloid Progenitor (CMP). Megakaryocytes and erythrocytes derive from the Megakaryocyte-Erythrocyte Progenitor (MEP), also from the CMP.

What are the general characteristics of hematopoietic growth factors (cytokines)?

Growth factors are diverse cytokines produced by many cell types. They regulate hematopoiesis (survival, proliferation, differentiation) and act via specific receptors. They are categorized as early-acting (multilineage) or later-acting (lineage-restricted).

Identify major examples of early-acting (multilineage) hematopoietic growth factors.

SCF (Stem Cell Factor / KIT Ligand), FL (Flt3 Ligand), IL-3, IL-6, IL-11.

Identify major examples of later-acting (lineage-restricted) hematopoietic growth factors.

EPO (Erythropoietin) for erythroid lineage, TPO (Thrombopoietin) for megakaryocyte lineage, G-CSF (Granulocyte Colony-Stimulating Factor) for granulocytes, M-CSF (Macrophage Colony-Stimulating Factor) for monocytes, and GM-CSF (Granulocyte-Macrophage Colony-Stimulating Factor) for granulocytes and macrophages.

What are the primary pathways of cytokine regulation in hematopoiesis?

1. Paracrine signaling: Cytokines act on nearby cells.
2. Juxtacrine signaling: Signaling requires direct cell-to-cell contact.

List two possibilities hematopoiesis may be negatively regulated.

1. Direct inhibition by cytokines: Such as Interferons (INF), Transforming Growth Factor-β (TGF-β), and TNF-α (Tumor Necrosis Factor-α) which limit proliferation and differentiation.
2. Apoptosis induction: Some negative regulators like TNF-α can promote programmed cell death in certain hematopoietic contexts.

Identify the major growth factors involved in various stages of hematopoiesis.

1. Early-acting/Multilineage: SCF, FL, IL-3, IL-6, IL-11.
2. Lineage-specific: EPO (erythroid), TPO (megakaryocyte/platelets), G-CSF (granulocytes), M-CSF (monocytes), GM-CSF (granulocytes/macrophages).

Precursor Cells

Cells that are more differentiated than stem cells but not fully mature, committed to a particular lineage, and capable of further proliferation and differentiation into mature blood cells. Includes progenitors (e.g., CMP, CLP) and blasts.