| Literature DB >> 26084022 |
Arnav Mehta1, Jimmy L Zhao1, Nikita Sinha2, Georgi K Marinov2, Mati Mann2, Monika S Kowalczyk3, Rachel P Galimidi2, Xiaomi Du2, Erdem Erikci4, Aviv Regev5, Kamal Chowdhury4, David Baltimore6.
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.Entities:
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Year: 2015 PMID： 26084022 PMCID： PMC4471877 DOI： 10.1016/j.immuni.2015.05.017
Source DB: PubMed Journal: Immunity ISSN： 1074-7613 Impact factor: 31.745