Transcriptional accessibility for genes of multiple tissues and hematopoietic lineages is hierarchically controlled during early hematopoiesis

Hematopoietic stem cells (HSCs) maintain hernatopoiesis by giving rise to all types of blood cells. Recent reports suggest that HSCs also possess the potential to generate nonhematopoietic tissues. To evaluate the underlying mechanisms in the commitment of HSCs into multitissue and multilhematopoietic lineages, we performed oligonucleotide array analyses targeting for prospectively purified HSCs, multipotent progenitors (MPPs), common lymphold progenitors (CLPs), and common myeloid progenitors (CMPs). Here we show that HSCs coexpress multiple nonhematopoletic genes as well as hematopoietic genes; MPPs coexpress myeloid and lymphold genes; CMPs,coexpress myeloerythroid, but not lymphoid genes, whereas CLPs coexpress T-, B-, and natural killer-lymphoid, but not myeloid, genes. Thus, the stepwise decrease in transcriptional accessibility for multilineage-affiliated genes may represent progressive restriction of developmental potentials in early hematopoiesis. These data support the hypothesis that stem cells possess a wide-open chromatin structure to maintain their multipotentiality, which is progressively quenched as they go down a particular pathway of differentiation. (Blood. 2003;101:383-390) (C) 2003 by The American Society of Hematology