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Proc Natl Acad Sci U S A. 2014 May 27;111(21):7695-700. doi: 10.1073/pnas.1400128111. Epub 2014 May 12.

YY1 is indispensable for Lgr5+ intestinal stem cell renewal.

Author information

1
Department of Genetics, Human Genetics Institute of New Jersey, Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, Piscataway, NJ 08854; and.
2
Department of Biological Sciences, Rutgers, The State University of New Jersey, Newark, NJ 07102.
3
Department of Genetics, Human Genetics Institute of New Jersey, Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, Piscataway, NJ 08854; and mverzi@gmail.com.

Abstract

The intestinal stem cell fuels the highest rate of tissue turnover in the body and has been implicated in intestinal disease and cancer; understanding the regulatory mechanisms controlling intestinal stem cell physiology is of great importance. Here, we provide evidence that the transcription factor YY1 is essential for intestinal stem cell renewal. We observe that YY1 loss skews normal homeostatic cell turnover, with an increase in proliferating crypt cells and a decrease in their differentiated villous progeny. Increased crypt cell numbers come at the expense of Lgr5(+) stem cells. On YY1 deletion, Lgr5(+) cells accelerate their commitment to the differentiated population, exhibit increased levels of apoptosis, and fail to maintain stem cell renewal. Loss of Yy1 in the intestine is ultimately fatal. Mechanistically, YY1 seems to play a role in stem cell energy metabolism, with mitochondrial complex I genes bound directly by YY1 and their transcript levels decreasing on YY1 loss. These unappreciated YY1 functions broaden our understanding of metabolic regulation in intestinal stem cell homeostasis.

KEYWORDS:

crypt base columnar cell; mitochondria; transcriptional regulation

PMID:
24821761
PMCID:
PMC4040551
DOI:
10.1073/pnas.1400128111
[Indexed for MEDLINE]
Free PMC Article

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