HES-1 preserves purified hematopoietic stem cells ex vivo and accumulates side population cells in vivo - PubMed (original) (raw)

. 2003 Mar 1;101(5):1777-83.

doi: 10.1182/blood-2002-07-2051. Epub 2002 Oct 24.

Shigeru Chiba, Etsuko Nakagami-Yamaguchi, Keiki Kumano, Toshiki Saito, Shigeo Masuda, Tomoyuki Yamaguchi, Masatake Osawa, Ryoichiro Kageyama, Hiromitsu Nakauchi, Mitsuo Nishikawa, Hisamaru Hirai

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• PMID: 12406868
• DOI: 10.1182/blood-2002-07-2051

Free article

HES-1 preserves purified hematopoietic stem cells ex vivo and accumulates side population cells in vivo

Atsushi Kunisato et al. Blood. 2003.

Free article

Abstract

Mouse long-term hematopoietic reconstituting cells exist in the c-Kit+Sca-1+Lin- (KSL) cell population; among them, CD34(low/-) cells represent the most highly purified population of hematopoietic stem cells in the adult bone marrow. Here, we demonstrate that retrovirus-mediated transduction of CD34(low/-)c-Kit+Sca-1+Lin- (34-KSL) cells with the HES-1 gene, which encodes a basic helix-loop-helix transcription factor functioning downstream of the Notch receptor, and is a key molecule for the growth phase of neural stem cells in the embryo, preserves the long-term reconstituting activity of these cells in vitro. We also show that cells derived from the HES-1-transduced 34-KSL population produce progenies characterized by negative Hoechst dye staining, which defines the side population, and by CD34(low/-) profile in the bone marrow KSL population in each recipient mouse at ratios 3.5- and 7.8-fold those produced by nontransduced 34-KSL-derived competitor cells. We conclude that HES-1 preserves the long-term reconstituting hematopoietic activity of 34-KSL stem cells ex vivo. Up-regulation of HES-1 protein in the 34-KSL population before unnecessary cell division, that is, without retrovirus transduction, may represent a potent approach to absolute expansion of hematopoietic stem cells.

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