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Deletion of the Imprinted Gene Grb10 Promotes Hematopoietic Stem Cell Self-Renewal and Regeneration.

Publication ,  Journal Article
Yan, X; Himburg, HA; Pohl, K; Quarmyne, M; Tran, E; Zhang, Y; Fang, T; Kan, J; Chao, NJ; Zhao, L; Doan, PL; Chute, JP
Published in: Cell Rep
November 1, 2016

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 in vivo.

Duke Scholars

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Published In

Cell Rep

DOI

EISSN

2211-1247

Publication Date

November 1, 2016

Volume

17

Issue

6

Start / End Page

1584 / 1594

Location

United States

Related Subject Headings

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

Citation

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Yan, X., Himburg, H. A., Pohl, K., Quarmyne, M., Tran, E., Zhang, Y., … Chute, J. P. (2016). Deletion of the Imprinted Gene Grb10 Promotes Hematopoietic Stem Cell Self-Renewal and Regeneration. Cell Rep, 17(6), 1584–1594. https://doi.org/10.1016/j.celrep.2016.10.025
Yan, Xiao, Heather A. Himburg, Katherine Pohl, Mamle Quarmyne, Evelyn Tran, Yurun Zhang, Tiancheng Fang, et al. “Deletion of the Imprinted Gene Grb10 Promotes Hematopoietic Stem Cell Self-Renewal and Regeneration.Cell Rep 17, no. 6 (November 1, 2016): 1584–94. https://doi.org/10.1016/j.celrep.2016.10.025.
Yan X, Himburg HA, Pohl K, Quarmyne M, Tran E, Zhang Y, et al. Deletion of the Imprinted Gene Grb10 Promotes Hematopoietic Stem Cell Self-Renewal and Regeneration. Cell Rep. 2016 Nov 1;17(6):1584–94.
Yan, Xiao, et al. “Deletion of the Imprinted Gene Grb10 Promotes Hematopoietic Stem Cell Self-Renewal and Regeneration.Cell Rep, vol. 17, no. 6, Nov. 2016, pp. 1584–94. Pubmed, doi:10.1016/j.celrep.2016.10.025.
Yan X, Himburg HA, Pohl K, Quarmyne M, Tran E, Zhang Y, Fang T, Kan J, Chao NJ, Zhao L, Doan PL, Chute JP. Deletion of the Imprinted Gene Grb10 Promotes Hematopoietic Stem Cell Self-Renewal and Regeneration. Cell Rep. 2016 Nov 1;17(6):1584–1594.
Journal cover image

Published In

Cell Rep

DOI

EISSN

2211-1247

Publication Date

November 1, 2016

Volume

17

Issue

6

Start / End Page

1584 / 1594

Location

United States

Related Subject Headings

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