The MicroRNA-132 and MicroRNA-212 Cluster Regulates Hematopoietic Stem Cell Maintenance and Survival with Age by Buffering FOXO3 Expression
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Regev_The microRNA.pdf
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Author(s)
Mehta, Arnav
Zhao, Jimmy L.
Sinha, Nikita
Marinov, Georgi K.
Mann, Mati
Kowalczyk, Monika S.
Galimidi, Rachel P.
Du, Xiaomi
Erikci, Erdem
Chowdhury, Kamal
Date Issued
May 2015
Journal
Immunity
Publisher
Elsevier/Cell Press
Citation
Mehta, Arnav et al. “The MicroRNA-132 and MicroRNA-212 Cluster Regulates Hematopoietic Stem Cell Maintenance and Survival with Age by Buffering FOXO3 Expression.” Immunity 42.6 (2015): 1021–1032.
Version
Author's final manuscript
Abstract
MicroRNAs are critical post-transcriptional regulators of hematopoietic cell-fate decisions, though little remains known about their role in aging hematopoietic stem cells (HSCs). We found that the regulated during aging. Both over-expression and deletion of microRNAs in this cluster leads to inappropriate hematopoiesis with age. Enforced expression of miR-132 in the bone marrow of mice led to rapid HSC cycling and depletion. A genetic deletion of Mirc19 in mice resulted in HSCs that had altered cycling, function, and survival in response to growth factor starvation. We found that miR-132 exerted its effect on aging HSCs by targeting the transcription factor FOXO3, a known aging associated gene. Our data demonstrates that Mirc19 plays a role in maintaining balanced hematopoietic output by buffering FOXO3 expression. We have thus identified it as a potential target that may play a role in age-related hematopoietic defects.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/j.immuni.2015.05.017
