Hematopoiesis

Hematopoiesis is the continuous, regulated process of blood cell production from pluripotent hematopoietic stem cells (HSCs) in the bone marrow. HSCs possess the unique properties of self-renewal and multilineage differentiation potential. Through a hierarchy of committed progenitor cells, HSCs give rise to all mature blood cell lineages via two major pathways: the myeloid lineage (common myeloid progenitor producing erythrocytes, platelets, granulocytes, and monocytes) and the lymphoid lineage (common lymphoid progenitor producing B lymphocytes, T lymphocytes, and NK cells). Erythropoiesis is driven primarily by erythropoietin (EPO) produced by peritubular interstitial cells of the kidney in response to hypoxia via HIF (hypoxia-inducible factor) signaling. EPO binds to receptors on erythroid progenitors (BFU-E and CFU-E), promoting survival, proliferation, and terminal differentiation through the reticulocyte stage. Thrombopoiesis is regulated by thrombopoietin (TPO), produced constitutively by the liver, which drives megakaryocyte proliferation and maturation; each megakaryocyte undergoes endomitosis (nuclear replication without cell division) and releases 1,000-3,000 platelets. Granulopoiesis is regulated by G-CSF and GM-CSF, which stimulate neutrophil production and can be administered therapeutically (filgrastim) for chemotherapy-induced neutropenia. The bone marrow microenvironment (niche) provides essential signals...