Article

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

Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI 53226, USA.
Journal of Experimental Medicine (Impact Factor: 13.91). 05/2011; 208(5):923-35. DOI: 10.1084/jem.20101192
Source: PubMed

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.

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Available from: Demin Wang, Aug 07, 2015
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    • "In rats the loss of Gimap5 function is milder, as a premature termination in Gimap5 of the BioBreeding rat results only in a T-cell lymphopenia , which is a susceptibility factor for autoimmunity in this diabetic rodent model (Hornum et al. 2002; MacMurray et al. 2002). Both Gimap3 and Gimap5 have been shown to interact with Bcl2 family members (Nitta et al. 2006; Chen et al. 2011), although the function of these interactions on membrane surfaces has yet to be elucidated. Here, we investigated in more detail the basis by which Gimap3 is important for mtDNA segregation in the mouse hematopoietic compartment. "
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