The MicroRNA-132 and MicroRNA-212 Cluster Regulates Hematopoietic Stem Cell Maintenance and Survival with Age by Buffering FOXO3 Expression
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; Baltimore, David; Regev, Aviv; ... Show more Show less![Thumbnail](/bitstream/handle/1721.1/105744/Regev_The%20microRNA.pdf.jpg?sequence=4&isAllowed=y)
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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.
Date issued
2015-05Department
Massachusetts Institute of Technology. Department of BiologyJournal
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
ISSN
1097-4180
1074-7613