YY1 is indispensable for Lgr5+ intestinal stem cell renewal

Ansu O. Perekatt, Michael J. Valdez, Melanie Davila, A. Hoffman, Edward M. Bonder, Nan Gao, Michael P. Verzi

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

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 homeo-static 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.

Original languageEnglish (US)
Pages (from-to)7695-7700
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number21
DOIs
StatePublished - May 27 2014

All Science Journal Classification (ASJC) codes

  • General

Keywords

  • Crypt base columnar cell
  • Mitochondria
  • Transcriptional regulation

Fingerprint

Dive into the research topics of 'YY1 is indispensable for Lgr5+ intestinal stem cell renewal'. Together they form a unique fingerprint.

Cite this