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Prepublished online as a Blood First Edition Paper on March 6, 2003March 13, 2003; DOI 10.1182/blood-2002-08-2509.

Submitted August 23, 2002
Accepted January 28, 2003
Gene expression analysis of purified hematopoietic stem cells and committed progenitors
Alexey V Terskikh*, Toshihiro Miyamoto, Cynthia Chang, Luda Diatchenko, and Irving L Weissman
Department of Pathology and Developmental Biology, Stanford University, Stanford, CA, USA
Clontech Laboratories Inc, PaloAlto, CA, USA
* Corresponding author; email: terskikh{at}burnham.edu.
Life-long self-renewal is a unique property of somatic stem cells. Recently, several primitive multipotent yet committed (non self-renewing) hematopoietic progenitor populations were identified in mouse bone marrow. We have characterized the expression of 1200 selected mouse genes using the Atlas cDNA array in highly purified hematopoietic stem cells (HSCs) and six closely related progenitor populations, CMPs. GMPs, MEPs, CLPs, pro-T and pro-B cells. Cluster analysis revealed that nearly half of all differentially expressed transcripts are associated with HSCs, supporting the notion of an active transcriptional status of HSCs. Genes found enriched in the HSC cluster encompass many developmentally regulated genes, some previously associated with HSC self-renewal. In contrast, genes that are enriched in committed progenitors, are mostly associated with hematopoietic differentiation, immune regulation and metabolism. Thus the transition from HSCs towards committed progenitors, correlates with the downregulation of a large number of HSC associated genes and progressive upregulation of a limited number of lineage-specific genes. These genetic analyses revealed both quantitative and qualitative differences between the transcripts associated with HSCs versus downstream progenitors and produced a list of the candidate genes, potentially involved in HSCs self-renewal.

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