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J Exp Med. 2011 May 9;208(5):923-35. doi: 10.1084/jem.20101192. Epub 2011 Apr 18.

Critical role for Gimap5 in the survival of mouse hematopoietic stem and progenitor cells.

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1
Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI 53226, USA.

Abstract

Mice and rats lacking the guanosine nucleotide-binding protein Gimap5 exhibit peripheral T cell lymphopenia, and Gimap5 can bind to Bcl-2. We show that Gimap5-deficient mice showed progressive multilineage failure of bone marrow and hematopoiesis. Compared with wild-type counterparts, Gimap5-deficient mice contained more hematopoietic stem cells (HSCs) but fewer lineage-committed hematopoietic progenitors. The reduction of progenitors and differentiated cells in Gimap5-deficient mice resulted in a loss of HSC quiescence. Gimap5-deficient HSCs and progenitors underwent more apoptosis and exhibited defective long-term repopulation capacity. Absence of Gimap5 disrupted interaction between Mcl-1-which is essential for HSC survival-and HSC70, enhanced Mcl-1 degradation, and compromised mitochondrial integrity in progenitor cells. Thus, Gimap5 is an important stabilizer of mouse hematopoietic progenitor cell survival.

PMID:
21502331
PMCID:
PMC3092340
DOI:
10.1084/jem.20101192
[Indexed for MEDLINE]
Free PMC Article
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