Published in: Blood, 15 January 2003, Vol. 101, No. 2, pp. 383-389
http://www.bloodjournal.org/cgi/content/abstract/101/2/383?etoc
Blood First Edition Paper
prepublished online September 5, 2002; DOI 10.1182/blood-2002-06-1780

"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. 


Abstract:

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.


Additional References:

1. Manz MG, Miaymoto T, Akashi K, and Weissman IL, "Prospective Isolation of Human Clonogenic Common Myeloid Progenitors". Proc. Natl. Acad. Sci. USA, vol. 99, no. 18, pp. 11872-11877 (September 3, 2002).

2. Nakatsu SL, Masek MA, Landrum S, and Frenster JH, "Activity of DNA Templates during Cell Division and Cell Differentiation", Nature vol. 248, no. 5446, pp. 334-335 (March 22, 1974).

3. Frenster JH, Nakatsu SL, and Masek MA, "Ultrastructural Probes of DNA Templates within Human Bone
Marrow and Lymph Node Cells", Adv Cell Molec Biol 3, 1-19 (1974), ed. DuPraw EJ, New York: Academic Press.

4. Hovsepian JA, and Frenster JH, "RNA-Induced Melting of DNA during Selective Gene Transcription", Molec. Biol. Cell, vol. 13, supp. p. 239a (November, 2002).

5. Frenster JH, "Ultrastructural Probes of Active DNA Sites, and the RNA Activators of DNA", Slide Presentation with Review Papers.
 


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