MicroRNA programs in normal and aberrant stem and progenitor cells
- Christopher P. Arnold1,2,
- Ruoying Tan3,
- Baiyu Zhou4,
- Si-Biao Yue1,2,
- Steven Schaffert1,2,
- Joseph R. Biggs5,
- Regis Doyonnas1,2,
- Miao-Chia Lo5,
- John M. Perry6,
- Valérie M. Renault7,
- Alessandra Sacco1,2,8,
- Tim Somervaille9,
- Patrick Viatour10,
- Anne Brunet7,
- Michael L. Cleary9,
- Linheng Li6,11,
- Julien Sage7,10,
- Dong-Er Zhang5,
- Helen M. Blau1,2,
- Caifu Chen3 and
- Chang-Zheng Chen1,2,12
- 1Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California 94305, USA;
- 2Baxter Laboratory for Stem Cell Biology, Stanford University School of Medicine, Stanford, California 94305, USA;
- 3Life Technologies, Molecular Biology Systems Division, Foster City, California 94404, USA;
- 4Department of Statistics, Stanford University, Stanford, California 94305, USA;
- 5Moores Cancer Center, University of California San Diego, La Jolla, California 92093, USA;
- 6Stowers Institute for Medical Research, Kansas City, Missouri 64110, USA;
- 7Department of Genetics, Stanford University School of Medicine, Stanford, California 94305, USA;
- 8Muscle Development and Regeneration Program, Sanford Children's Health Research Center, Sanford-Burnham Medical Research Institute, La Jolla, California 92037, USA;
- 9Department of Pathology, Stanford University School of Medicine, Stanford, California 94305, USA;
- 10Department of Pediatrics, Stanford University School of Medicine, Stanford, California 94305, USA;
- 11Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, Kansas 66160, USA
Abstract
Emerging evidence suggests that microRNAs (miRNAs), an abundant class of ∼22-nucleotide small regulatory RNAs, play key roles in controlling the post-transcriptional genetic programs in stem and progenitor cells. Here we systematically examined miRNA expression profiles in various adult tissue-specific stem cells and their differentiated counterparts. These analyses revealed miRNA programs that are common or unique to blood, muscle, and neural stem cell populations and miRNA signatures that mark the transitions from self-renewing and quiescent stem cells to proliferative and differentiating progenitor cells. Moreover, we identified a stem/progenitor transition miRNA (SPT-miRNA) signature that predicts the effects of genetic perturbations, such as loss of PTEN and the Rb family, AML1-ETO9a expression, and MLL-AF10 transformation, on self-renewal and proliferation potentials of mutant stem/progenitor cells. We showed that some of the SPT-miRNAs control the self-renewal of embryonic stem cells and the reconstitution potential of hematopoietic stem cells (HSCs). Finally, we demonstrated that SPT-miRNAs coordinately regulate genes that are known to play roles in controlling HSC self-renewal, such as Hoxb6 and Hoxa4. Together, these analyses reveal the miRNA programs that may control key processes in normal and aberrant stem and progenitor cells, setting the foundations for dissecting post-transcriptional regulatory networks in stem cells.
Footnotes
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↵12 Corresponding author.
E-mail czchen{at}stanford.edu.
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[Supplemental material is available for this article. The microRNA expression data from this study have been submitted to the NCBI Gene Expression Omnibus (http://www.ncbi.nlm.nih.gov/geo/) under accession no. GSE28036.]
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Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.111385.110.
- Received June 6, 2010.
- Accepted February 7, 2011.
- Copyright © 2011 by Cold Spring Harbor Laboratory Press
