Suppression of progenitor differentiation requires the long noncoding RNA ANCR
- Markus Kretz1,2,5,
- Dan E. Webster2,5,
- Ross J. Flockhart2,
- Carolyn S. Lee2,
- Ashley Zehnder2,
- Vanessa Lopez-Pajares2,
- Kun Qu2,
- Grace X.Y. Zheng2,
- Jennifer Chow2,
- Grace E. Kim2,
- John L. Rinn3,
- Howard Y. Chang2,4,
- Zurab Siprashvili2 and
- Paul A. Khavari1,2,6
- 1Veterans Affairs Palo Alto Healthcare System, Palo Alto, California 94304, USA;
- 2The Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California 94305, USA;
- 3Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA;
- 4Howard Hughes Medical Institute, Stanford, California 94305, USA
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↵5 These authors contributed equally to this work.
Abstract
Long noncoding RNAs (lncRNAs) regulate diverse processes, yet a potential role for lncRNAs in maintaining the undifferentiated state in somatic tissue progenitor cells remains uncharacterized. We used transcriptome sequencing and tiling arrays to compare lncRNA expression in epidermal progenitor populations versus differentiating cells. We identified ANCR (anti-differentiation ncRNA) as an 855-base-pair lncRNA down-regulated during differentiation. Depleting ANCR in progenitor-containing populations, without any other stimuli, led to rapid differentiation gene induction. In epidermis, ANCR loss abolished the normal exclusion of differentiation from the progenitor-containing compartment. The ANCR lncRNA is thus required to enforce the undifferentiated cell state within epidermis.
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Footnotes
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↵6 Corresponding author.
E-mail khavari{at}stanford.edu.
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Supplemental material is available for this article.
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Article published online ahead of print. Article and publication date are online at http://www.genesdev.org/cgi/doi/10.1101/gad.182121.111.
- Received October 28, 2011.
- Accepted January 4, 2012.
- Copyright © 2012 by Cold Spring Harbor Laboratory Press