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 ste m cells (HSCs) is influenced by specific microenvironments, adult mous e bone marrow-derived HSCs were injected into mouse blastocysts. Embry os developing from injected blastocysts contained donor-derived cells at various developmental stages, and progeny of the stem cells were de tected in hematopoietic tissues. Thus, HSCs derived from an adult anim al survive after injection into blastocysts and are able to participat e in hematopoietic development. We further find that the erythroid pro geny of transplanted adult HSCs express embryonic/fetal-type globin ge nes and, conversely, that embryonic and fetal progenitor cells transpl anted into adult recipients transcribe the adult-type globin gene. Thu s, the developmental potential of adult HSCs is evidently more plastic than previously thought, and the developmental stage of the hematopoi etic microenvironment controls the developmental fate of transplanted progenitor cells.