MOLECULAR EVIDENCE THAT IN SITU-TRANSDUCED FETAL LIVER HEMATOPOIETIC STEM PROGENITOR CELLS GIVE RISE TO MEDULLARY HEMATOPOIESIS IN ADULT-RATS/

We exploited the ability to transduce fetal liver hematopoietic stem/p rogenitor cells in situ with recombinant retrovirus, together with the ability to analyze proviral integration patterns into chromosomal DNA , to detect the cellular and organ fate of hematopoietic stem and prog enitor-derived progeny in tissues and in the circulation of neonatal a nd adult rats. Two hundred seventeen fetuses were injected with retrov irus supernatant on day 16 of gestation, before the development of the bone marrow cavity. The progeny of 41 stem and progenitor cells from 97 liveborn rats were clonally identified. Pluripotent and lineage-res tricted stem/progenitor clones derived from the fetal liver consistent ly gave rise to progeny in the marrow of newborn and adult rats. Patte rns of differentiation of transduced stem and progenitor cells fell in to distinct subsets. Blood cells derived from in situ transduced cells that originated in the fetal liver circulated throughout the life spa n of the adult animals. These data provide molecular evidence of the o rigin of medullary cavity hematopoiesis by cells derived from the feta l liver that were transduced in vivo, homed to the developing medullar y cavity and proliferated in a normal medullary hematopoietic microenv ironment. (C) 1995 by The American Society of Hematology.