Biochemistry of Hematopoiesis

Transcription factors are key mediators of hematopoiesis. During development, SCL and GATA-2 direct formation of the hemangioblast, and RUNX1 subsequently specifies adult hematopoietic stem cells (HSCs). HSCs are maintained by TEL, MLL, and c-Myb and also give rise to the megakaryocyte-erythroid progenitor under direction of GATA-1 or to the lymphoid-myeloid progenitor (LMP) under direction of PU.1. GATA-1 together with EKLF, SCL, and NF-E2 further specify the erythroid lineage, whereas RUNX1 along with the Ets factors Fli-1 and ERG direct megakaryopoiesis. Lymphoid specification is initiated from the LMP by Ikaros. Subsequent B-cell development is mediated by EBF, E2A, Pax-5, and PU.1; with T-cell development occurring under direction of GATA-3 and Notch-1. RUNX1 contributes to CTL and Treg formation. C/EBPα initiates myelopoiesis from the LMP. C/EBPα increases PU.1 expression, zippers with AP-1 proteins, and cooperates with Egr-1 and ERK signals induced by M-CSF or other cytokines to direct monopoiesis. Alternatively, C/EBPα cooperates with Gfi-1, RARα, C/EBPα, STAT3, NF-κB p50, and increased SHP2 activity induced by G-CSF to mediate granulopoiesis. Coexpression of C/EBPκ and GATA-2 in GMP specifies the eosinophils, basophils, and mast cell lineages dependent on their order of expression. Monocytes generate macrophages, osteoclasts, or myeloid dendritic cells.