Title: MiR-29a maintains mouse hematopoietic stem cell self-renewal by regulating Dnmt3a
Authors: Hu, Wenhuo ×
Dooley, James
Chung, Stephen S
Chandramohan, Dhruva
Cimmino, Luisa
Mukherjee, Siddhartha
Mason, Christopher E
De Strooper, Bart
Liston, Adrian
Park, Christopher Y #
Issue Date: Apr-2015
Publisher: W.B. Saunders
Series Title: Blood vol:125 issue:14 pages:2206-16
Article number: blood-2014-06-585273
Abstract: Hematopoietic stem cells (HSCs) possess the ability to generate all hematopoietic cell types as well as 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, since miR-29b expression is unaltered in miR-29a/b-1 null HSCs, and only ectopic expression of miR-29a restores HSPC 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 shRNA 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.
ISSN: 0006-4971
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Genetics of Autoimmunity
Department of Human Genetics - miscellaneous
× corresponding author
# (joint) last author

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