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Prepublished online as a Blood First Edition Paper on September 5, 2002; DOI 10.1182/blood-2002-06-1780.
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Blood, 15 January 2003, Vol. 101, No. 2, pp. 383-389
PLENARY PAPER
Transcriptional accessibility for genes of multiple tissues and
hematopoietic lineages 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
From the Department of Cancer Immunology and AIDS,
Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA;
Stowers Institute for Medical Research, Kansas City, MO; and Department
of Mathematics and Statistics, University of Missouri, Kansas City.
Hematopoietic stem cells (HSCs) maintain hematopoiesis 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 multihematopoietic 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 coexpress multiple
nonhematopoietic genes as well as hematopoietic genes; MPPs coexpress
myeloid and lymphoid 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.

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