miR-29a maintains mouse hematopoietic stem cell self-renewal by regulating Dnmt3a Journal Article
| Authors: | Hu, W.; Dooley, J.; Chung, S. S.; Chandramohan, D.; Cimmino, L.; Mukherjee, S.; Mason, C. E.; De Strooper, B.; Liston, A.; Park, C. Y. |
| Article Title: | miR-29a maintains mouse hematopoietic stem cell self-renewal by regulating Dnmt3a |
| Abstract: | Hematopoietic stem cells (HSCs) possess the ability to generate all hematopoietic cell types and to self-renew over long periods, but the mechanisms that regulate their unique properties are incompletely understood. Herein, we show that homozygous deletion of the miR-29a/b-1 bicistron results in decreased numbers of hematopoietic stem and progenitor cells (HSPCs), decreased HSC self-renewal, and increased HSC cell cycling and apoptosis. The HSPC phenotype is specifically due to loss of miR-29a, because miR-29b expression is unaltered in miR-29a/b-1- null HSCs, and only ectopic expression of miR-29a restoresHSPC function both in vitro and in vivo. HSCs lacking miR-29a/b-1 exhibit widespread transcriptional dysregulation and adopt gene expression patterns similar to normal committed progenitors. A number of predicted miR-29 target genes, including Dnmt3a, are significantly upregulated in miR-29a/b-1-null HSCs. The loss of negative regulation of Dnmt3a by miR-29a is a major contributor to the miR-29a/b-1-null HSPC phenotype, as both in vitro Dnmt3a short hairpin RNA knockdown assays and a genetic haploinsufficiency model of Dnmt3a restored the frequency and long-term reconstitution capacity of HSCs from miR-29a/b-1-deficient mice. Overall, these data demonstrate that miR-29a is critical for maintaining HSC function through its negative regulation of Dnmt3a. © 2015 by The American Society of Hematology. |
| Journal Title: | Blood |
| Volume: | 125 |
| Issue: | 14 |
| ISSN: | 0006-4971 |
| Publisher: | American Society of Hematology |
| Date Published: | 2015-04-02 |
| Start Page: | 2206 |
| End Page: | 2216 |
| Language: | English |
| DOI: | 10.1182/blood-2014-06-585273 |
| PROVIDER: | scopus |
| PMCID: | PMC4383797 |
| PUBMED: | 25634742 |
| DOI/URL: | |
| Notes: | Export Date: 4 May 2015 -- Source: Scopus |
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