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

Immunity
Authors
Keywords
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 microRNA-212/132 cluster (Mirc19) is enriched in HSCs and is upregulated during aging. Both overexpression 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 demonstrate that Mirc19 plays a role in maintaining balanced hematopoietic output by buffering FOXO3 expression. We have thus identified it as a potential target that might play a role in age-related hematopoietic defects.

Year of Publication
2015
Journal
Immunity
Volume
42
Issue
6
Pages
1021-32
Date Published
2015 Jun 16
ISSN
1097-4180
URL
DOI
10.1016/j.immuni.2015.05.017
PubMed ID
26084022
PubMed Central ID
PMC4471877
Links
Grant list
CA183220 / CA / NCI NIH HHS / United States
R01AI079243 / AI / NIAID NIH HHS / United States
R01 AI079243 / AI / NIAID NIH HHS / United States
F30 HL110691 / HL / NHLBI NIH HHS / United States
HL110691 / HL / NHLBI NIH HHS / United States
F30 CA183220 / CA / NCI NIH HHS / United States