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Prepublished online as a Blood First Edition Paper on September 5, 2002; DOI 10.1182/blood-2002-06-1780. This Article Full Text (PDF) All Versions of this Article: 2002-06-1780v1 101/2/383    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Akashi, K. Articles by Li, L. Search for Related Content PubMed PubMed Citation Articles by Akashi, K. Articles by Li, L. Social Bookmarking                   What's this? Submitted June 17, 2002 Accepted August 14, 2002 Transcriptional accessibility for multi-tissue and multi-hematopoietic lineage genes is hierarchically controlled during early hematopoiesis Koichi Akashi, Xi He, Jie Chen, Hiromi Iwasaki, Chao Niu, Brooke Steenhard, Jiwang Zhang, Jeff Haug, and Linheng Li* Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA Stowers Institute for Medical Research, Kansas City, MO, USA Department of Mathematics and Statistics, University of Missouri-Kansas City, Kansas City, MO, USA * Corresponding author; email: lil{at}stowers-institute.org. Hematopoietic stem cells (HSCs) maintain hematopoiesis by giving rise to all types of blood cells. Recent reports suggest that HSCs also possess potential to generate non-hematopoietic tissues. To evaluate the underlying mechanisms in the commitment of HSCs into multi-tissue and multi-hematopoietic lineages, we performed oligonucleotide array analyses targeting for prospectively purified HSCs, multipotent progenitors (MPPs), common lymphoid progenitors (CLPs), and common myeloid progenitors (CMPs). Here we show that HSCs co-express multiple non-hematopoietic genes as well as hematopoietic genes; MPPs co-express myeloid and lymphoid genes; CMPs coexpress myelo-erythroid, but not lymphoid genes, whereas CLPs co-express T, B and NK lymphoid, but not myeloid genes. Thus, the stepwise decrease in transcriptional accessibility for multiple lineage-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. 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