In vivo differentiation of stem cells in the aorta-gonad-mesonephros region of mouse embryo and adult bone marrow.

OBJECTIVE: Hematopoietic stem cells (HSCs) are thought to be generated from hemangioblasts, the common precursor cells for blood and endothelial cells, in the aorta-gonad-mesonephros (AGM) region of the mouse embryo. The genetic program of HSCs was recently demonstrated to be plastic, but the potential for AGM-region hemangioblasts to be transplanted and to differentiate in vivo has not been well described. Here we examined the fate of donor cells in mice transplanted with CD45(-) AGM cells, which presumably include hemangioblasts.

MATERIALS AND METHODS: CD45(-) cells in the AGM region of embryos at 11.5 days post coitum or CD45(+)CD34(-) side population (SP) of cells in adult bone marrow (BM) derived from enhanced green fluorescent protein transgenic mice were transplanted into the liver of busulfan-treated neonatal mice. Two to 6 months after injection of the cells, the contribution of donor-derived cells in the hematopoietic compartment and in various organs was analyzed by flow cytometry and confocal microscopy.

RESULTS: CD45(-) cells from the AGM region not only generated peripheral blood cells but also differentiated into endothelial and other nonhematopoietic cells in liver, kidney, lung, small intestine, and uterus in transplanted mice. A similar engrafting pattern was observed in the small intestine of mice transplanted with BM SP/CD45(+) cells, secondary BM-transplanted mice, and lethally irradiated adult mice that received intravenous injections of BM cells.

CONCLUSION: A CD45(-) fraction of the AGM region and CD45(+) BM stem cells share the same in vivo potential to differentiate into hematopoietic, endothelial, smooth muscle, and stroma-like cells when transplanted in mice.