Hematopoiesis: Stem Cells to Circulating Cells
Hematopoiesis: from stem cell to circulating cell
Hematopoiesis is hierarchical. Long-term repopulating hematopoietic stem cells (HSCs) reside in perivascular and endosteal niches, held quiescent by CXCL12/CXCR4, Notch, and TGF-β signaling, and balanced between self-renewal and differentiation. Downstream multipotent and committed progenitors (CMP, CLP, MEP, GMP) expand under lineage-specific factors: erythropoietin for erythroid, G-CSF for granulocytic, thrombopoietin for megakaryocytic, and IL-7 for lymphoid development. Ontogeny moves from yolk sac to fetal liver to bone marrow, which becomes the dominant site by the third trimester.
Marrow cellularity declines with age; a rough rule is cellularity ≈ 100 − age in percent, ±20%. Normal marrow contains myeloid and erythroid cells at roughly 2:1 to 4:1, plus megakaryocytes, lymphocytes, plasma cells, and stroma. Maturation follows orderly, recognizable sequences. Erythroid: proerythroblast → basophilic → polychromatophilic → orthochromatophilic normoblast → reticulocyte → erythrocyte; the nucleus is extruded before release, and the reticulocyte retains RNA for about one to two days. Granulocytic: myeloblast → promyelocyte → myelocyte → metamyelocyte → band → segmented neutrophil, with the myelocyte as the last dividing stage. Neutrophils exist in circulating and marginated pools that interconvert within minutes under stress or epinephrine, without new production. Egress depends on CXCR4–CXCL12 gradients and sphingosine-1-phosphate.
Trap: an "immature" marrow in a child or young adult may be normal, whereas a hypercellular marrow in an older adult is not; always compare with age-matched expectations.
Rule of thumb: cellularity ≈ 100 − age. A 70-year-old with 80% cellularity has a hypercellular marrow deserving explanation.