title: Polycomb Complex PRC1 Preserves Intestinal Stem Cell Identity by Sustaining Wnt/β-Catenin Transcriptional Activity.
abstract: Polycomb repressive complexes (PRCs) are among the most important gatekeepers of establishing and maintaining cell identity in metazoans. PRC1, which plays a dominant role in this context, executes its functions via multiple subcomplexes, which all contribute to H2AK119 mono-ubiquitination (H2Aubq). Despite our comprehensive knowledge of PRC1-dependent H2Aubq in embryonic stem cells and during early development, its role in adult stem cells still remains poorly characterized. Here we show that PRC1 activity is required for the integrity of the intestinal epithelium, regulating stem cell self-renewal via a cell-autonomous mechanism that is independent from Cdkn2a expression. By dissecting the PRC1-dependent transcription program in intestinal stem cells, we demonstrate that PRC1 represses a large number of non-lineage-specific transcription factors that directly affect β-catenin/Tcf transcriptional activity. Our data reveal that PRC1 preserves Wnt/β-catenin activity in adult stem cells to maintain intestinal homeostasis and supports tumor formation induced by the constitutive activation of this pathway.
authors.affiliation: Department of Experimental Oncology, European Institute of Oncology, Via Adamello 16, 20139 Milan, Italy.
authors.forename: Fulvio
authors.initials: F
authors.lastname: Chiacchiera
authors.affiliation: Department of Experimental Oncology, European Institute of Oncology, Via Adamello 16, 20139 Milan, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Rossi
authors.affiliation: Department of Experimental Oncology, European Institute of Oncology, Via Adamello 16, 20139 Milan, Italy.
authors.forename: SriGanesh
authors.initials: S
authors.lastname: Jammula
authors.affiliation: Department of Experimental Oncology, European Institute of Oncology, Via Adamello 16, 20139 Milan, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Piunti
authors.affiliation: Department of Experimental Oncology, European Institute of Oncology, Via Adamello 16, 20139 Milan, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Scelfo
authors.affiliation: École Polytechnique Fédérale de Lausanne (EPFL), ISREC, Lausanne CH-1015, Switzerland.
authors.forename: Paloma
authors.initials: P
authors.lastname: Ordóñez-Morán
authors.affiliation: École Polytechnique Fédérale de Lausanne (EPFL), ISREC, Lausanne CH-1015, Switzerland.
authors.forename: Joerg
authors.initials: J
authors.lastname: Huelsken
authors.affiliation: Developmental Genetics Group, RIKEN Research Centre for Allergy & Immunology (RCAI), 1-7-22 Suehiuro-cho, Tsurumi, Yokohama, Kanagawa 230-0045, Japan.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Koseki
authors.affiliation: Department of Experimental Oncology, European Institute of Oncology, Via Adamello 16, 20139 Milan, Italy. Electronic address: diego.pasini@ieo.eu.
authors.forename: Diego
authors.initials: D
authors.lastname: Pasini
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology*; D000483:Alleles; D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006706:Homeostasis; D007422:Intestines / Q000166:cytology*; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D063146:Polycomb-Group Proteins / Q000378:metabolism*; D014018:Tissue Distribution; D014158:Transcription, Genetic; D051153:Wnt Proteins / Q000378:metabolism*; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D063146:Polycomb-Group Proteins; D051153:Wnt Proteins; D051176:beta Catenin; D049452:Green Fluorescent Proteins