title: YY1 is indispensable for Lgr5+ intestinal stem cell renewal.
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.
authors.affiliation: 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.
authors.forename: Ansu O
authors.initials: AO
authors.lastname: Perekatt
authors.affiliation: 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.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Valdez
authors.affiliation: 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.
authors.forename: Melanie
authors.initials: M
authors.lastname: Davila
authors.affiliation: 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.
authors.forename: A
authors.initials: A
authors.lastname: Hoffman
authors.affiliation: Department of Biological Sciences, Rutgers, The State University of New Jersey, Newark, NJ 07102.
authors.forename: Edward M
authors.initials: EM
authors.lastname: Bonder
authors.affiliation: Department of Biological Sciences, Rutgers, The State University of New Jersey, Newark, NJ 07102.
authors.forename: Nan
authors.initials: N
authors.lastname: Gao
authors.affiliation: 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.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Verzi
mesh_terms: D000818:Animals; D002455:Cell Division / Q000502:physiology*; D047369:Chromatin Immunoprecipitation; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000502:physiology*; D007422:Intestines / Q000166:cytology*; D051379:Mice; D018345:Mice, Knockout; D046228:Microarray Analysis; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000378:metabolism / Q000502:physiology*; D050986:YY1 Transcription Factor / Q000235:genetics / Q000378:metabolism*
chemical_list: D050986:YY1 Transcription Factor
keywords: crypt base columnar cell; mitochondria; transcriptional regulation