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TISSUE-SPECIFIC STEM CELLS

E2F-6 Suppresses Growth-Associated Apoptosis of Human Hematopoietic Progenitor Cells by Counteracting Proapoptotic Activity of E2F-1

^aDivision of Stem Cell Regulation, Center for Molecular Medicine, and
^cDivision of Hematology, Department of Internal Medicine, Jichi Medical School, Shimotsuke, Tochigi, Japan; and
^bCell Regulation Analysis Team, Research Center for Glycoscience, National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki, Japan

Key Words. E2F • Hematopoietic progenitor cell • Apoptosis • Transcription

Correspondence: Yusuke Furukawa, M.D., Division of Stem Cell Regulation, Center for Molecular Medicine, Jichi Medical School, 3311-1 Yakushiji, Shimotsuke-City, Tochigi 329-0498, Japan. Telephone: 81-285-58-7400; Fax: 81-285-44-7501; e-mail: furuyu{at}jichi.ac.jp

Received on March 27, 2007; accepted for publication on June 18, 2007.

First published online in STEM CELLS EXPRESS  June 28, 2007.


E2F-6 is a dominant-negative transcriptional repressor against other members of the E2F family. In this study, we investigated the expression and function of E2F-6 in human hematopoietic progenitor cells to clarify its role in hematopoiesis. We found that among E2F subunits, E2F-1, E2F-2, E2F-4, and E2F-6 were expressed in CD34⁺ human hematopoietic progenitor cells. The expression of E2F-6 increased along with proliferation and decreased during differentiation of hematopoietic progenitors, whereas the other three species were upregulated in CD34^– bone marrow mononuclear cells. Overexpression of E2F-6 did not affect the growth of immature hematopoietic cell line K562 but suppressed E2F-1-induced apoptosis, whereas it failed to inhibit apoptosis induced by differentiation inducers and anticancer drugs. Among E2F-1-dependent apoptosis-related molecules, E2F-6 specifically inhibited upregulation of Apaf-1 by competing with E2F-1 for promoter binding. E2F-6 similarly suppressed apoptosis and Apaf-1 upregulation in primary hematopoietic progenitor cells during cytokine-induced proliferation but had no effect when they were differentiated. As a result, E2F-6 enhanced the clonogenic growth of colony-forming unit-granulocyte, erythroid, macrophage, and megakaryocyte. These results suggest that E2F-6 provides a failsafe mechanism against loss of hematopoietic progenitor cells during proliferation.

Disclosure of potential conflicts of interest is found at the end of this article.

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