During ontogeny primitive (CD34(+)CD38(-)) hematopoietic cells show altered expression of a subset of genes associated with early cytokine and differentiation responses of their adult counterparts

Comparison of gene expression profiles in closely related subpopulations of primitive hematopoietic cells offers a powerful first step to elucidating the molecular basis of their different biologic properties. Here we present the results of a comparative quantitative analysis of transcript levels fo r various growth factor receptors, ligands, and transcription factor genes in CD34(+)CD38(-) and CD34(+)CD38(+) cells purified from first trimester hu man fetal liver, cord blood, and adult bone marrow (BM). In addition, adult BM CD34(+)CD38(-) cells were examined after short-term exposure to various growth factors in vitro. Transcripts for 19 of the 24 genes analyzed were detected in unmanipulated adult BM CD34(+)CD38(-) cells. Moreover, the leve ls of transforming growth factor beta (TGF-beta), gp130, c-fos, and c-jun t ranscripts in these cells were consistently and significantly different (hi gher) than in all other populations analyzed, including phenotypically simi lar but biologically different cells from fetal or neonatal sources, as wel l as adult BM CD34(+) cells still in G(0) after 2 days of growth factor sti mulation. We have thus identified a subset of early response genes whose ex pression in primitive human hematopoietic cells is differently regulated du ring ontogeny and in a fashion that is recapitulated in growth factor-stimu lated adult BM CD34(+)CD38(-) cells, before their cell cycle progression an d independent of their subsequent differentiation response. These findings suggest a progressive alteration in the physiology of primitive hematopoiet ic cells during development such that these cells initially display a parti ally "activated" state, which is not maximally repressed until after birth. (C) 2000 by The American Society of Hematology.