The MicroRNA-132 and MicroRNA-212 Cluster Regulates Hematopoietic Stem Cell Maintenance and Survival with Age by Buffering FOXO3 Expression

• Main Authors: Mehta, Arnav (Author), Zhao, Jimmy L (Author), Sinha, Nikita (Author), Marinov, Georgi K (Author), Mann, Mati (Author), Kowalczyk, Monika S (Author), Galimidi, Rachel P (Author), Du, Xiaomi (Author), Erikci, Erdem (Author), Chowdhury, Kamal (Author), Baltimore, David (Author), Regev, Aviv (Contributor)
• Other Authors: Massachusetts Institute of Technology. Department of Biology (Contributor)
• Format: Article
• Language: English
• Published: Elsevier/Cell Press, 2016-12-07T20:25:09Z.
• Subjects: Article
• Online Access: Get fulltext

 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.