Hematopoiesis

• yolk - sac phase: hematopoiesis begins in the 3rd week of gestation, formation of “blood islands” (3-8 weeks) • hepatic phase - major blood forming organ in 2nd trimester • bone marrow phase - begins during 2nd trimester

• myeloid stem cells give rise to GEMM: • granulocytes (BEN) • erythrocyte • monocyte • megakarocytes • thrombocyte • lymphoid stem cell • T cell • B cell

• microenvironment in which HSCs are housed and maintained by allowing self renewal in the absence of differentiation • functions of stem cell niche: • storage of quiescent stem cells • self renewal • inhibition of differentiation • found in the epiphysial region of bones

• quiescent HSCs detach from the endosteal niche and migrate towards the center of the bone marrow to the vascular zone from where they establish hematopoiesis

• structure: reticular fibers, veins, arteries, sinusoids (type of capillaries), islands of cells • red marrow: active hematopoiesis • yellow marrow: fat, capillaries, reticular cells, inactive hematopoeisis

• erythropoietin (EPO) • stimulate production of erthyrocytes • thrombopoietin (TPO) • stimulate production of megakaryocytes –> thrombocytes • GM-CSF • granulocytes • interleukin-7 • lymphocytes (B and T cells)

main stimulus is hypoxia, 3-5 days to complete development erythropoietin - produced by kidney • proerythroblast: no hemoglobin, large nucleus, basophilic • basophilic erythroblast: some hemoglobin, condensing nucleus • polychromatophilic erythroblast: • orthochromatophilic erythroblast: increased hemoglobin • reticulocyte: no nucleus, some ribosomes • erythrocyte: only hemoglobin, no ribosomes

• myeloblast • precursor cells • promyelocyte • Golgi appears, granules form • myelocyte • specific granules are produced, where cell type is determined • metamyelocyte

• monoblasts • promonocytes • monocytes: kidney shaped nucleus • enter the circulation, proceed to tissue spaces, differentiate into macrophages

• controlled by thrombopoietin (TPO) produced by liver • megakaryoblast: • megakaryocyte: large multi-lobed nucleus • platelets are formed from fragments of megakaryocyte

• lymphoblasts: large, undifferentiated cells • prolymphocytes: medium-sized cells, condensing chromatin, no cell surface antigens • some migrate from bone marrow to thymus, divide and differentiate into T-cells • others remain in bone marrow, differentiate to B-cells, migrate to lymph tissues