Journal article
Modest Declines in Proteome Quality Impair Hematopoietic Stem Cell Self-Renewal
Lorena Hidalgo San Jose, Mary Jean Sunshine, Christopher H Dillingham, Bernadette A Chua, Miriama Kruta, Yuning Hong, Danny M Hatters, Robert AJ Signer
Cell Reports | Elsevier | Published : 2020
Abstract
Low protein synthesis is a feature of somatic stem cells that promotes regeneration in multiple tissues. Modest increases in protein synthesis impair stem cell function, but the mechanisms by which this occurs are largely unknown. We determine that low protein synthesis within hematopoietic stem cells (HSCs) is associated with elevated proteome quality in vivo. HSCs contain less misfolded and unfolded proteins than myeloid progenitors. Increases in protein synthesis cause HSCs to accumulate misfolded and unfolded proteins. To test how proteome quality affects HSCs, we examine Aarssti/sti mice that harbor a tRNA editing defect that increases amino acid misincorporation. Aarssti/sti mice exhib..
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Grants
Awarded by NIH/NIDDK
Awarded by V Foundation for Cancer Research
Awarded by American Cancer Society Institutional Research Grant
Awarded by UCSD Moores Cancer Center - NIH/NCI Specialized Cancer Center Support Grant
Awarded by NIH Shared Instrumentation Grant Program
Funding Acknowledgements
We would like to thank E.J. Bennett, M. Leonard, S.A. Ackerman, J.S. Gutkind, S.J. Morrison, and J.A. Magee, C. Kim and the staff at the LJI Flow Cytometry core facility, J. Day and S. Wlodychak at the LJI NGS core facility, and J. Greenbaum and A. Chawla at the LJI Bioinformatics core facility. This work was supported by the NIH/NIDDK (R01DK116951), Scholar Awards from the V Foundation for Cancer Research (V2017-003) and the American Society of Hematology, the American Cancer Society Institutional Research Grant (IRG-15-172-45-IRG), the Sanford Stem Cell Clinical Center, and the UCSD Moores Cancer Center, which is supported by the NIH/NCI Specialized Cancer Center Support Grant (2P30CA023100-33). The LJI Flow Cytometry core facility is supported by the NIH Shared Instrumentation Grant Program (S10 RR027366). L.H.S.J. was supported by a Chancellor's Research Excellence Scholarship.