SCL/TAL1 in Hematopoiesis and Cellular Reprogramming.

摘要: SCL, a transcription factor of the basic helix-loop-helix family, is master regulator hematopoiesis. Scl specifies lateral plate mesoderm to hematopoietic fate and establishes boundaries by inhibiting cardiac lineage. A combinatorial interaction between Vegfa/Flk1 sets in motion first wave primitive Subsequently, definitive stem cells (HSCs) emerge from embryo proper via an endothelial-to-hematopoietic transition controlled Runx1, acting with Gata2. Past this stage, steady state HSCs redundant Lyl1, highly homologous factor. However, haploinsufficient stress response, when rare subpopulation very long term repopulating capacity called into action. SCL activates recruiting core complex on DNA that necessarily includes E2A/HEB, GATA1-3, LIM-only proteins LMO1/2, LDB1, extended comprising ETO2, RUNX1, ERG, or FLI1. These interactions confer multifunctionality can control cell proliferation erythroid progenitors commitment terminal differentiation through variations single component. Ectopic LMO1/2 expression immature thymocytes gene network reprogram finite lifespan self-renewing preleukemic (pre-LSCs), initiating event T-cell acute lymphoblastic leukemias. Interestingly, conversion fibroblasts hematoendothelial requires not only Lmo2 but also Gata2, Erg, indicating necessary collaboration these factors for reprogramming. Nonetheless, full reprogramming multipotent may require additional most likely, permissive microenvironment.