PMID- 18536716 OWN - NLM STAT- MEDLINE DCOM- 20080722 LR - 20220330 IS - 1546-1718 (Electronic) IS - 1061-4036 (Print) IS - 1061-4036 (Linking) VI - 40 IP - 7 DP - 2008 Jul TI - Bmi1 is expressed in vivo in intestinal stem cells. PG - 915-20 LID - 10.1038/ng.165 [doi] AB - Bmi1 plays an essential part in the self-renewal of hematopoietic and neural stem cells. To investigate its role in other adult stem cell populations, we generated a mouse expressing a tamoxifen-inducible Cre from the Bmi1 locus. We found that Bmi1 is expressed in discrete cells located near the bottom of crypts in the small intestine, predominantly four cells above the base of the crypt (+4 position). Over time, these cells proliferate, expand, self-renew and give rise to all the differentiated cell lineages of the small intestine epithelium. The induction of a stable form of beta-catenin in these cells was sufficient to rapidly generate adenomas. Moreover, ablation of Bmi1(+) cells using a Rosa26 conditional allele, expressing diphtheria toxin, led to crypt loss. These experiments identify Bmi1 as an intestinal stem cell marker in vivo. Unexpectedly, the distribution of Bmi1-expressing stem cells along the length of the small intestine suggested that mammals use more than one molecularly distinguishable adult stem cell subpopulation to maintain organ homeostasis. FAU - Sangiorgi, Eugenio AU - Sangiorgi E AD - Howard Hughes Medical Institute and Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, Utah 84112, USA. FAU - Capecchi, Mario R AU - Capecchi MR LA - eng GR - R01 GM021168/GM/NIGMS NIH HHS/United States GR - R01 GM021168-34/GM/NIGMS NIH HHS/United States GR - HHMI/Howard Hughes Medical Institute/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20080608 PL - United States TA - Nat Genet JT - Nature genetics JID - 9216904 RN - 0 (Bmi1 protein, mouse) RN - 0 (Nuclear Proteins) RN - 0 (Proto-Oncogene Proteins) RN - 0 (Repressor Proteins) RN - EC 2.3.2.27 (Polycomb Repressive Complex 1) SB - IM CIN - Nat Genet. 2008 Jul;40(7):818-9. doi: 10.1038/ng0708-818. PMID: 18583974 MH - Adult Stem Cells/*metabolism MH - Animals MH - Homeostasis/physiology MH - Intestinal Mucosa/*metabolism MH - Intestines/cytology/physiology MH - Lac Operon MH - Mice MH - Mice, Transgenic MH - Nuclear Proteins/genetics/*metabolism MH - Polycomb Repressive Complex 1 MH - Proto-Oncogene Proteins/genetics/*metabolism MH - Repressor Proteins/genetics/*metabolism MH - Tissue Distribution PMC - PMC2906135 MID - NIHMS128707 EDAT- 2008/06/10 09:00 MHDA- 2008/07/23 09:00 PMCR- 2010/07/19 CRDT- 2008/06/10 09:00 PHST- 2008/02/12 00:00 [received] PHST- 2008/04/02 00:00 [accepted] PHST- 2008/06/10 09:00 [pubmed] PHST- 2008/07/23 09:00 [medline] PHST- 2008/06/10 09:00 [entrez] PHST- 2010/07/19 00:00 [pmc-release] AID - ng.165 [pii] AID - 10.1038/ng.165 [doi] PST - ppublish SO - Nat Genet. 2008 Jul;40(7):915-20. doi: 10.1038/ng.165. Epub 2008 Jun 8.