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Critical role for Gimap5 in the survival of mouse hematopoietic stem and progenitor cells. J Exp Med 2011 May 09;208(5):923-35

Date

04/20/2011

Pubmed ID

21502331

Pubmed Central ID

PMC3092340

DOI

10.1084/jem.20101192

Scopus ID

2-s2.0-79956105663   26 Citations

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.

Author List

Chen Y, Yu M, Dai X, Zogg M, Wen R, Weiler H, Wang D

Authors

Demin Wang PhD Assistant Professor in the Microbiology and Immunology department at Medical College of Wisconsin
Hartmut Weiler PhD Associate Professor in the Physiology department at Medical College of Wisconsin
Renren Wen PhD Associate Investigator in the Blood Research Institute department at BloodCenter of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Apoptosis
Cell Line
Cell Survival
GTP Phosphohydrolases
HSC70 Heat-Shock Proteins
Hematopoietic Stem Cells
Lymphopenia
Mice
Mice, Mutant Strains
Mitochondria
Myeloid Cell Leukemia Sequence 1 Protein
Proto-Oncogene Proteins c-bcl-2
Rats
T-Lymphocytes
jenkins-FCD Prod-469 c3fc8ab87196149f9b23743c01b947d47e7319e5