Transcriptomics

Dataset Information

3

MicroRNA expression in murine hematopoietic stem cells


ABSTRACT: MicroRNAs influence hematopoietic differentiation, but little is known about their effects on the stem cell state. Here, we report that the microRNA processing enzyme Dicer is essential for stem cell persistence in vivo and a specific microRNA, miR-125a controls the size of the stem cell population by regulating stem/progenitor cell (HSPC) apoptosis. Conditional deletion of Dicer revealed an absolute dependence for the multipotent HSPC population in a cell autonomous manner, with increased HSPC apoptosis in mutant animals. An evolutionarily conserved microRNA cluster containing miR-99b, let-7e and miR-125a was preferentially expressed in long term HSCs. miR-125a alone was capable of increasing the number of hematopoietic stem cells in vivo by more than eight fold. This was accomplished through a differentiation stage-specific reduction of apoptosis in immature hematopoietic progenitors, possibly through targeting multiple pro-apoptotic genes. Bak1 was directly down-regulated by miR-125a and expression of a 3’UTR-less Bak1 blocked miR-125a-induced hematopoietic expansion in vivo. These data demonstrate cell-state-specific regulation by microRNA and identify a unique microRNA functioning to regulate the stem cell pool size. Bone marrow populations were FACS-sorted and profiled using a bead-based profiling platform. Long-term HSCs, short-term HSCs, multipotent progenitors, Lin-Kit+Sca+ cells, Lin-Kit+Sca- cells, Lin-Kit-Sca+ cells, Lin- cells and unfractionated whole bone marrow cells were prepared for total RNA using TriZol (Invitrogen) in replicates. For rare populations, cells from multiple mice were pooled. To perform microRNA profiling, 60 ng of total RNA were used for each sample.

ORGANISM(S): Mus musculus  

SUBMITTER: Shangqin Guo   Todd R Golub  David T Scadden  Jun Lu 

PROVIDER: E-GEOD-22450 | ArrayExpress | 2010-08-14

SECONDARY ACCESSION(S): GSE22450PRJNA128535

REPOSITORIES: GEO, ArrayExpress

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Publications

MicroRNA miR-125a controls hematopoietic stem cell number.

Guo Shangqin S   Lu Jun J   Schlanger Rita R   Zhang Hao H   Wang Judy Y JY   Fox Michelle C MC   Purton Louise E LE   Fleming Heather H HH   Cobb Bradley B   Merkenschlager Matthias M   Golub Todd R TR   Scadden David T DT  

Proceedings of the National Academy of Sciences of the United States of America 20100708 32


MicroRNAs influence hematopoietic differentiation, but little is known about their effects on the stem cell state. Here, we report that the microRNA processing enzyme Dicer is essential for stem cell persistence in vivo and a specific microRNA, miR-125a, controls the size of the stem cell population by regulating hematopoietic stem/progenitor cell (HSPC) apoptosis. Conditional deletion of Dicer revealed an absolute dependence for the multipotent HSPC population in a cell-autonomous manner, with  ...[more]

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