title: ID1 is a functional marker for intestinal stem and progenitor cells required for normal response to injury.
abstract: LGR5 and BMI1 mark intestinal stem cells in crypt base columnar cells and +4 position cells, respectively, but characterization of functional markers in these cell populations is limited. ID1 maintains the stem cell potential of embryonic, neural, and long-term repopulating hematopoietic stem cells. Here, we show in both human and mouse intestine that ID1 is expressed in cycling columnar cells, +4 position cells, and transit-amplifying cells in the crypt. Lineage tracing revealed ID1+ cells to be self-renewing, multipotent stem/progenitor cells that are responsible for the long-term renewal of the intestinal epithelium. Single ID1+ cells can generate long-lived organoids resembling mature intestinal epithelium. Complete knockout of Id1 or selective deletion of Id1 in intestinal epithelium or in LGR5+ stem cells sensitizes mice to chemical-induced colon injury. These experiments identify ID1 as a marker for intestinal stem/progenitor cells and demonstrate a role for ID1 in maintaining the potential for repair in response to colonic injury.
authors.affiliation: Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA; Cancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Ning
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY 10065, USA.
authors.forename: Rhonda K
authors.initials: RK
authors.lastname: Yantiss
authors.affiliation: Cancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Hyung-Song
authors.initials: HS
authors.lastname: Nam
authors.affiliation: Cancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Yvette
authors.initials: Y
authors.lastname: Chin
authors.affiliation: Department of Healthcare Policy and Research, Weill Cornell Medical College, New York, NY 10065, USA.
authors.forename: Xi Kathy
authors.initials: XK
authors.lastname: Zhou
authors.affiliation: Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA.
authors.forename: Ellen J
authors.initials: EJ
authors.lastname: Scherl
authors.affiliation: Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA.
authors.forename: Brian P
authors.initials: BP
authors.lastname: Bosworth
authors.affiliation: Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA.
authors.forename: Kotha
authors.initials: K
authors.lastname: Subbaramaiah
authors.affiliation: Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA. Electronic address: ajdannen@med.cornell.edu.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Dannenberg
authors.affiliation: Cancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA. Electronic address: r-benezra@ski.mskcc.org.
authors.forename: Robert
authors.initials: R
authors.lastname: Benezra
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D049109:Cell Proliferation; D003092:Colitis / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D003106:Colon / Q000293:injuries / Q000378:metabolism; D016264:Dextran Sulfate; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D051798:Inhibitor of Differentiation Protein 1 / Q000235:genetics / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism*; D007422:Intestines / Q000166:cytology; D019394:Ki-67 Antigen / Q000378:metabolism; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008822:Mice, Transgenic; D039902:Multipotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D009940:Organoids / Q000166:cytology / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D015415:Biomarkers; C497453:ID1 protein, human; C497455:Idb1 protein, mouse; D051798:Inhibitor of Differentiation Protein 1; D019394:Ki-67 Antigen; C493597:Lgr5 protein, mouse; D043562:Receptors, G-Protein-Coupled; D016264:Dextran Sulfate