The Journal of Experimental Medicine
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Published online
doi:10.1084/jem.20080578
The Journal of Experimental Medicine, Vol. 205, No. 9, 2163-2175
The Rockefeller University Press, 0022-1007 $30.00
© Qian et al.
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ARTICLE

 A critical role for Apc in hematopoietic stem and progenitor cell survival

Zhijian Qian1, Lina Chen1, Anthony A. Fernald1, Bart O. Williams2, and Michelle M. Le Beau1

1 Section of Hematology/Oncology and the Cancer Research Center, University of Chicago, Chicago, IL 60637
2 Laboratory of Cell Signaling and Carcinogenesis, Van Andel Research Institute, Grand Rapids, MI 49503

CORRESPONDENCE Zhijian Qian: zqian{at}bsd.uchicago.edu

The adenomatous polyposis coli (Apc) tumor suppressor is involved in the initiation and progression of colorectal cancer via regulation of the Wnt signaling cascade. In addition, Apc plays an important role in multiple cellular functions, including cell migration and adhesion, spindle assembly, and chromosome segregation. However, its role during adult hematopoiesis is unknown. We show that conditional inactivation of Apc in vivo dramatically increases apoptosis and enhances cell cycle entry of hematopoietic stem cells (HSCs)/ hematopoietic progenitor cells (HPCs), leading to their rapid disappearance and bone marrow failure. The defect in HSCs/HPCs caused by Apc ablation is cell autonomous. In addition, we found that loss of Apc leads to exhaustion of the myeloid progenitor pool (common myeloid progenitor, granulocyte-monocyte progenitor, and megakaryocyte-erythroid progenitor), as well as the lymphoid-primed multipotent progenitor pool. Down-regulation of the genes encoding Cdkn1a, Cdkn1b, and Mcl1 occurs after acute Apc excision in candidate HSC populations. Together, our data demonstrate that Apc is essential for HSC and HPC maintenance and survival.

Abbreviations used: APC, adenomatous polyposis coli; CAFC, cobblestone area–forming cell; CLP, common lymphoid progenitor; CM, chimeric mice; CMP, common myeloid progenitor; GMP, granulocyte-monocyte progenitor; HPC, hematopoietic progenitor cell; HSC, hematopoietic stem cell; LMPP, lymphoid-primed multipotent progenitor pool; MEP, megakaryocyte-erythroid progenitor; PB, peripheral blood; pI-pC, polyinosinic-polycytidylic acid; qRT-PCR, quantitative RT-PCR.

© 2008 Qian et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).


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