Made with Xodo PDF Reader and Editor
Hematopoiesis
Executive Summary
Hematopoiesis is the process of making all blood cells in the bone marrow 1 . Embryologically, it starts
in the yolk sac (week 3), moves to the fetal liver and spleen (months 2–3), and finally takes place in the
bone marrow by about 5 months of gestation 1 . After birth, active red marrow is mainly in flat bones
and the ends of long bones 1 2 . A single hematopoietic stem cell can make RBCs (carry oxygen),
WBCs (fight infection), and platelets (help clot blood) 3 . Red cells live ~120 days; neutrophils live ~1–2
days; platelets ~5–9 days 4 . Important factors: EPO (from kidney) drives RBC production 5 ; TPO
(from liver) drives platelet production 6 ; G-CSF drives neutrophils; IL-7 drives lymphocytes; GATA1 (a
transcription factor) drives RBC/megakaryocyte development 7 ; PU.1 drives myeloid cells 8 .
Diseases include various anemias, leukemias (e.g. ALL, AML, CML), myeloproliferative disorders,
myelodysplasia, hemoglobin disorders, and low blood cell counts. Diagnostics: CBC, reticulocyte count,
marrow biopsy/aspirate, immunophenotyping (flow cytometry), cytogenetics/molecular tests.
Figure: Hematopoietic differentiation diagram (primitive stem cell → all blood lineages) 7 8 .
Definition
Hematopoiesis (hemopoiesis) is the formation of blood cells. It occurs mainly in the bone marrow in
adults 1 . Hematopoietic stem cells (HSCs) in the marrow can renew themselves and produce all blood
cell types (RBCs, WBCs, platelets) 3 . Each type of blood cell develops from these stem cells through a
series of steps (see Lineage pathways).
Embryology (Developmental Sites)
• Week 3: Blood cell production begins in the yolk sac (primitive erythroblasts).
• Months 2–3: The liver and spleen become the main hematopoietic organs, producing RBCs,
platelets, and WBCs. The thymus also begins making T-cells.
• ~Month 5: Bone marrow takes over as the major site of hematopoiesis 1 .
• After Birth: Active marrow remains in the axial skeleton (sternum, ribs, pelvis, vertebrae) and
proximal long bones (femur, humerus) 1 .
Bone Marrow Anatomy and Histology
• The bone marrow fills the spongy cavities of bone. It has red marrow (active, blood-forming)
and yellow marrow (fatty, inactive) 2 .
• Red marrow contains developing blood cells at all stages, along with fat cells, fibroblasts,
macrophages, and blood vessels. Yellow marrow has mostly fat. Adults have about 50%
hematopoietic cells and 50% fat in marrow (this ratio changes with age).
• Supporting cells (stroma) include osteoblasts (on bone surfaces), sinusoidal endothelial cells,
adipocytes, and mesenchymal stem cells. These stromal cells help create the microenvironment
(niche) for HSCs 9 . The marrow’s rich blood supply (sinusoids) allows mature cells to enter
circulation easily.
1
, Made with Xodo PDF Reader and Editor
Hematopoietic Stem Cell (HSC) Biology
• Definition: HSCs are rare, primitive cells in marrow that give rise to all blood cells 3 . They are
multipotent (can become many cell types) and can self-renew.
• Phenotype (Markers): Human HSCs are usually identified as Lineage-negative, CD34 positive,
CD38 negative (Lin⁻ CD34⁺ CD38⁻) 3 . This means they do not express mature blood cell
markers (Lin⁻) but do express CD34. As cells differentiate, they lose CD34 and gain other
markers.
• Self-Renewal vs. Differentiation: HSCs must balance making more stem cells (self-renewal) and
making progenitors that will differentiate. This balance is tightly controlled. Differentiation
occurs in steps: stem cell → multipotent progenitor → lineage-committed progenitor →
precursor cell → mature cell.
• Niche (Microenvironment): HSCs live in specific areas (niches) in the marrow. Two key niches
are:
• Endosteal niche: near bone surface with osteoblasts; maintains HSC quiescence.
• Perivascular niche: near blood vessels, with endothelial cells and stromal (MSC) cells. This niche
produces factors like SCF (stem cell factor) and CXCL12 to support HSC survival 10 .
Low oxygen (hypoxia) in marrow helps keep HSCs inactive via HIF pathways.
Lineage Commitment (CMP vs CLP)
HSCs first split into two progenitors:
- Common Myeloid Progenitor (CMP): leads to myeloid lineages (RBCs, granulocytes, monocytes,
platelets).
- Common Lymphoid Progenitor (CLP): leads to lymphoid lineages (B-cells, T-cells, NK-cells).
This gives the main branches of blood cell development, described in detail below.
Erythropoiesis (Red Cell Development)
• Pathway: HSC → CMP → Erythroid progenitors (BFU-E/CFU-E) → Proerythroblast → Basophilic
erythroblast → Polychromatic erythroblast → Orthochromatic erythroblast → Reticulocyte → Red
blood cell (RBC).
• Markers: Early erythroid cells express CD71 (transferrin receptor) and glycophorin A (CD235a).
Mature RBCs have no nucleus and no markers.
• Regulation: Kidney-derived EPO stimulates proliferation and maturation of erythroid precursors
5 . EPO acts via JAK2/STAT signaling. Transcription factor GATA1 is essential for erythroid gene
expression 7 . Without GATA1, cells arrest at proerythroblast stage.
• Physiology: Healthy bone marrow produces ~200 billion RBCs per day. Normal RBC lifespan ≈
120 days 4 . Reticulocyte count (young RBCs) rises when production increases (e.g., after
bleeding).
Granulopoiesis and Monocytopoiesis (White Cell Development)
• Granulocytes (Neutrophils/Eosinophils/Basophils): HSC → CMP → Granulocyte-Monocyte
progenitor (GMP) → Myeloblast → Promyelocyte → Myelocyte → Metamyelocyte → Band cell →
Mature granulocyte. Neutrophils have segmented nuclei; eosinophils have red-staining granules;
basophils have large dark granules.
• Monocytes: HSC → CMP → GMP → Monoblast → Promonocyte → Monocyte → Tissue
macrophage. Monocytes have kidney-shaped nucleus and become macrophages in tissues.
2
Hematopoiesis
Executive Summary
Hematopoiesis is the process of making all blood cells in the bone marrow 1 . Embryologically, it starts
in the yolk sac (week 3), moves to the fetal liver and spleen (months 2–3), and finally takes place in the
bone marrow by about 5 months of gestation 1 . After birth, active red marrow is mainly in flat bones
and the ends of long bones 1 2 . A single hematopoietic stem cell can make RBCs (carry oxygen),
WBCs (fight infection), and platelets (help clot blood) 3 . Red cells live ~120 days; neutrophils live ~1–2
days; platelets ~5–9 days 4 . Important factors: EPO (from kidney) drives RBC production 5 ; TPO
(from liver) drives platelet production 6 ; G-CSF drives neutrophils; IL-7 drives lymphocytes; GATA1 (a
transcription factor) drives RBC/megakaryocyte development 7 ; PU.1 drives myeloid cells 8 .
Diseases include various anemias, leukemias (e.g. ALL, AML, CML), myeloproliferative disorders,
myelodysplasia, hemoglobin disorders, and low blood cell counts. Diagnostics: CBC, reticulocyte count,
marrow biopsy/aspirate, immunophenotyping (flow cytometry), cytogenetics/molecular tests.
Figure: Hematopoietic differentiation diagram (primitive stem cell → all blood lineages) 7 8 .
Definition
Hematopoiesis (hemopoiesis) is the formation of blood cells. It occurs mainly in the bone marrow in
adults 1 . Hematopoietic stem cells (HSCs) in the marrow can renew themselves and produce all blood
cell types (RBCs, WBCs, platelets) 3 . Each type of blood cell develops from these stem cells through a
series of steps (see Lineage pathways).
Embryology (Developmental Sites)
• Week 3: Blood cell production begins in the yolk sac (primitive erythroblasts).
• Months 2–3: The liver and spleen become the main hematopoietic organs, producing RBCs,
platelets, and WBCs. The thymus also begins making T-cells.
• ~Month 5: Bone marrow takes over as the major site of hematopoiesis 1 .
• After Birth: Active marrow remains in the axial skeleton (sternum, ribs, pelvis, vertebrae) and
proximal long bones (femur, humerus) 1 .
Bone Marrow Anatomy and Histology
• The bone marrow fills the spongy cavities of bone. It has red marrow (active, blood-forming)
and yellow marrow (fatty, inactive) 2 .
• Red marrow contains developing blood cells at all stages, along with fat cells, fibroblasts,
macrophages, and blood vessels. Yellow marrow has mostly fat. Adults have about 50%
hematopoietic cells and 50% fat in marrow (this ratio changes with age).
• Supporting cells (stroma) include osteoblasts (on bone surfaces), sinusoidal endothelial cells,
adipocytes, and mesenchymal stem cells. These stromal cells help create the microenvironment
(niche) for HSCs 9 . The marrow’s rich blood supply (sinusoids) allows mature cells to enter
circulation easily.
1
, Made with Xodo PDF Reader and Editor
Hematopoietic Stem Cell (HSC) Biology
• Definition: HSCs are rare, primitive cells in marrow that give rise to all blood cells 3 . They are
multipotent (can become many cell types) and can self-renew.
• Phenotype (Markers): Human HSCs are usually identified as Lineage-negative, CD34 positive,
CD38 negative (Lin⁻ CD34⁺ CD38⁻) 3 . This means they do not express mature blood cell
markers (Lin⁻) but do express CD34. As cells differentiate, they lose CD34 and gain other
markers.
• Self-Renewal vs. Differentiation: HSCs must balance making more stem cells (self-renewal) and
making progenitors that will differentiate. This balance is tightly controlled. Differentiation
occurs in steps: stem cell → multipotent progenitor → lineage-committed progenitor →
precursor cell → mature cell.
• Niche (Microenvironment): HSCs live in specific areas (niches) in the marrow. Two key niches
are:
• Endosteal niche: near bone surface with osteoblasts; maintains HSC quiescence.
• Perivascular niche: near blood vessels, with endothelial cells and stromal (MSC) cells. This niche
produces factors like SCF (stem cell factor) and CXCL12 to support HSC survival 10 .
Low oxygen (hypoxia) in marrow helps keep HSCs inactive via HIF pathways.
Lineage Commitment (CMP vs CLP)
HSCs first split into two progenitors:
- Common Myeloid Progenitor (CMP): leads to myeloid lineages (RBCs, granulocytes, monocytes,
platelets).
- Common Lymphoid Progenitor (CLP): leads to lymphoid lineages (B-cells, T-cells, NK-cells).
This gives the main branches of blood cell development, described in detail below.
Erythropoiesis (Red Cell Development)
• Pathway: HSC → CMP → Erythroid progenitors (BFU-E/CFU-E) → Proerythroblast → Basophilic
erythroblast → Polychromatic erythroblast → Orthochromatic erythroblast → Reticulocyte → Red
blood cell (RBC).
• Markers: Early erythroid cells express CD71 (transferrin receptor) and glycophorin A (CD235a).
Mature RBCs have no nucleus and no markers.
• Regulation: Kidney-derived EPO stimulates proliferation and maturation of erythroid precursors
5 . EPO acts via JAK2/STAT signaling. Transcription factor GATA1 is essential for erythroid gene
expression 7 . Without GATA1, cells arrest at proerythroblast stage.
• Physiology: Healthy bone marrow produces ~200 billion RBCs per day. Normal RBC lifespan ≈
120 days 4 . Reticulocyte count (young RBCs) rises when production increases (e.g., after
bleeding).
Granulopoiesis and Monocytopoiesis (White Cell Development)
• Granulocytes (Neutrophils/Eosinophils/Basophils): HSC → CMP → Granulocyte-Monocyte
progenitor (GMP) → Myeloblast → Promyelocyte → Myelocyte → Metamyelocyte → Band cell →
Mature granulocyte. Neutrophils have segmented nuclei; eosinophils have red-staining granules;
basophils have large dark granules.
• Monocytes: HSC → CMP → GMP → Monoblast → Promonocyte → Monocyte → Tissue
macrophage. Monocytes have kidney-shaped nucleus and become macrophages in tissues.
2
