Globin Gene Expression Is Reprogrammed in Chimeras Generated by Injecting Adult Hematopoietic Stem Cells into Mouse Blastocysts

To elucidate whether the differentiation capacity of hematopoietic stem cells (HSCs) is influenced by specific microenvironments, adult mouse bone marrow-derived HSCs were injected into mouse blastocysts. Embryos developing from injected blastocysts contained donor-derived cells at various developmental stages, and progeny of the stem cells were detected in hematopoietic tissues. Thus, HSCs derived from an adult animal survive after injection into blastocysts and are able to participate in hematopoietic development. We further find that the erythroid progeny of transplanted adult HSCs express embryonic/fetal-type globin genes and, conversely, that embryonic and fetal progenitor cells transplanted into adult recipients transcribe the adult-type globin gene. Thus, the developmental potential of adult HSCs is evidently more plastic than previously thought, and the developmental stage of the hematopoietic microenvironment controls the developmental fate of transplanted progenitor cells.