Generation of definitive hematopoietic stem cells from murine early yolk sac and paraaortic splanchnopleures by aorta-gonad-mesonephros region-derived stromal cells

There is controversy as to whether murine definitive hematopoiesis originat es from yolk sac (YS) or the intraembryonic region. This study reports the generation of definitive hematopoietic stem cells (HSCs) from both early YS and infraembryonic paraaortic splanchnopleures (P-Sp) on AGM-S3 stromal ce lls derived from:the aorta-gonad-mesonephros (AGM) region at 10.5 days post coitum (dpc). YS and P-Sp cells at 8.5 dpc generated no definitive hematop oiesis-derived colony-forming cells in: cocultures with AGM-S3 cells, but s pleen colony-forming cells and HSCs capable of reconstituting definitive he matopoiesis In adult mice simultaneously appeared on day 4 of coculture. Pr ecursors for definitive HSCs were present in YS and P-Sp at 8.0 dpc, a time when YS and embryo were not connected by blood vessels. It is proposed tha t precursors with the potential to generate definitive HSCs appear independ ently in YS and intraembryonic P-Sp and that the P-Sp or AGM region affords the microenvironment that facilitates generation of definitive hematopoies is from precursors. (C) 2001 by The American Society of Hematology.