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Deletion of the Imprinted Gene Grb10 Promotes Hematopoietic Stem Cell Self-Renewal and Regeneration. Cell Rep 2016 11 01;17(6):1584-1594

Date

11/03/2016

Pubmed ID

27806297

Pubmed Central ID

PMC5963255

DOI

10.1016/j.celrep.2016.10.025

Scopus ID

2-s2.0-84995621461   17 Citations

Abstract

Imprinted genes are differentially expressed by adult stem cells, but their functions in regulating adult stem cell fate are incompletely understood. Here we show that growth factor receptor-bound protein 10 (Grb10), an imprinted gene, regulates hematopoietic stem cell (HSC) self-renewal and regeneration. Deletion of the maternal allele of Grb10 in mice (Grb10m/+ mice) substantially increased HSC long-term repopulating capacity, as compared to that of Grb10+/+ mice. After total body irradiation (TBI), Grb10m/+ mice demonstrated accelerated HSC regeneration and hematopoietic reconstitution, as compared to Grb10+/+ mice. Grb10-deficient HSCs displayed increased proliferation after competitive transplantation or TBI, commensurate with upregulation of CDK4 and Cyclin E. Furthermore, the enhanced HSC regeneration observed in Grb10-deficient mice was dependent on activation of the Akt/mTORC1 pathway. This study reveals a function for the imprinted gene Grb10 in regulating HSC self-renewal and regeneration and suggests that the inhibition of Grb10 can promote hematopoietic regeneration inA vivo.

Author List

Yan X, Himburg HA, Pohl K, Quarmyne M, Tran E, Zhang Y, Fang T, Kan J, Chao NJ, Zhao L, Doan PL, Chute JP

Author

Heather A. Himburg PhD Associate Professor in the Radiation Oncology department at Medical College of Wisconsin




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

Animals
Bone Marrow Cells
Cell Proliferation
Cell Self Renewal
GRB10 Adaptor Protein
Gene Deletion
Genomic Imprinting
Hematopoietic Stem Cells
Mechanistic Target of Rapamycin Complex 1
Mice, Inbred C57BL
Proto-Oncogene Proteins c-akt
Regeneration
Signal Transduction
Whole-Body Irradiation