title: Critical role for Gimap5 in the survival of mouse hematopoietic stem and progenitor cells.
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.
authors.affiliation: Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI 53226, USA.
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Chen
authors.forename: Mei
authors.initials: M
authors.lastname: Yu
authors.forename: Xuezhi
authors.initials: X
authors.lastname: Dai
authors.forename: Mark
authors.initials: M
authors.lastname: Zogg
authors.forename: Renren
authors.initials: R
authors.lastname: Wen
authors.forename: Hartmut
authors.initials: H
authors.lastname: Weiler
authors.forename: Demin
authors.initials: D
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002460:Cell Line; D002470:Cell Survival; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism*; D019204:GTP-Binding Proteins; D050883:HSC70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D008231:Lymphopenia / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D051381:Rats; D013601:T-Lymphocytes / Q000378:metabolism
chemical_list: C534135:Gimap5 protein, mouse; D050883:HSC70 Heat-Shock Proteins; C494372:Hspa8 protein, mouse; C579094:Mcl1 protein, mouse; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins