Deletion of the Imprinted Gene Grb10 Promotes Hematopoietic Stem Cell Self-Renewal and Regeneration
Open accessAbstract
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 ( Grb10 m/+ mice) substantially increased HSC long-term repopulating capacity, as compared to that of Grb10 +/+ mice. After total body irradiation (TBI), Grb10 m/+ 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.
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Studies of Grb10 deficient mice demonstrated Grb10's role in hematopoietic regeneration in vivo.
“Studies of Grb10 deficient mice demonstrated Grb10’s role in hematopoietic regeneration in vivo69.”
From Quantifying the contribution of Neanderthal introgression to the heritability of complex traits (2021) · cites this paper as [69]
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- Authors
- Yan, X., Himburg, H. A., Pohl, K., Quarmyne, M., Tran, E., Zhang, Y., Fang, T., Kan, J., Chao, N. J., Zhao, L., Doan, P. L., & Chute, J. P.
- Affiliations
- University of California, Los Angeles (US)
- Duke University (US)
- Corresponding author
- Chute, John P.
- ORCID
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2016-11
- Volume
- 17
- Issue
- 6
- Pages
- 1584-1594
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC5963255
- OpenAlex
- W2548044639
- Cited by
- 25
- References
- 43
- Citations by year
- 2026: 1 · 2025: 3 · 2023: 1 · 2022: 2 · 2021: 2 · 2020: 4 · 2019: 3 · 2018: 6 · 2017: 3
- FWCI
- 3.80
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- DukeSpace (Duke University) (submittedVersion, cc-by-nc-nd)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (NIAID) (AI067769)
- National Heart, Lung, and Blood Institute (NHLBI) (HL086998)
- California Institute for Regenerative Medicine (LA1-08014)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Syndromes and Imprinting
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Blood disorders and treatments
- Keywords
- Grb10, genomic imprinting, hematopoietic stem cells, stem cell self-renewal, hematopoietic regeneration, total body irradiation, hematopoietic recovery, CDK4, cyclin E, Akt/mTORC1 signaling, stem cell proliferation
- MeSH terms
- Cell Self Renewal, Mechanistic Target of Rapamycin Complex 1, Animals, Bone Marrow Cells, Hematopoietic Stem Cells, Mice, Inbred C57BL, Regeneration, Whole-Body Irradiation, Signal Transduction, Gene Deletion, Genomic Imprinting, Cell Proliferation, Proto-Oncogene Proteins c-akt, GRB10 Adaptor Protein
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