English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

The microRNA-132 and microRNA-212 cluster regulates hematopoietic stem cell maintenance and survival with age by buffering FOXO3 expression.

MPS-Authors
/persons/resource/persons73157

Erikci,  E.
Facility of Microarray Analyses, MPI for biophysical chemistry, Max Planck Society;

/persons/resource/persons14945

Chowdhury,  K.
Facility of Microarray Analyses, MPI for biophysical chemistry, Max Planck Society;

Fulltext (public)
There are no public fulltexts stored in PuRe
Supplementary Material (public)

2168364_Suppl_1.pdf
(Supplementary material), 4MB

2168364_Suppl_2.pdf
(Supplementary material), 6MB

Citation

Mehta, A., Zhao, J. L., Sinha, N., Marinov, G. K., Mann, M., Kowalczyk, M. S., et al. (2015). The microRNA-132 and microRNA-212 cluster regulates hematopoietic stem cell maintenance and survival with age by buffering FOXO3 expression. Immunity, 42(6), 1021-1032. doi:10.1016/j.immuni.2015.05.017.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0027-B0BC-0
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.