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Publication : The Lgr5 intestinal stem cell signature: robust expression of proposed quiescent '+4' cell markers.

First Author  Muñoz J Year  2012
Journal  EMBO J Volume  31
Issue  14 Pages  3079-91
PubMed ID  22692129 Mgi Jnum  J:186432
Mgi Id  MGI:5432307 Doi  10.1038/emboj.2012.166
Citation  Munoz J, et al. (2012) The Lgr5 intestinal stem cell signature: robust expression of proposed quiescent '+4' cell markers. EMBO J 31(14):3079-91
abstractText  Two types of stem cells are currently defined in small intestinal crypts: cycling crypt base columnar (CBC) cells and quiescent '+4' cells. Here, we combine transcriptomics with proteomics to define a definitive molecular signature for Lgr5(+) CBC cells. Transcriptional profiling of FACS-sorted Lgr5(+) stem cells and their daughters using two microarray platforms revealed an mRNA stem cell signature of 384 unique genes. Quantitative mass spectrometry on the same cell populations identified 278 proteins enriched in intestinal stem cells. The mRNA and protein data sets showed a high level of correlation and a combined signature of 510 stem cell-enriched genes was defined. Spatial expression patterns were further characterized by mRNA in-situ hybridization, revealing that approximately half of the genes were expressed in a gradient with highest levels at the crypt bottom, while the other half was expressed uniquely in Lgr5(+)stem cells. Lineage tracing using a newly established knock-in mouse for one of the signature genes, Smoc2, confirmed its stem cell specificity. Using this resource, we find-and confirm by independent approaches-that the proposed quiescent/'+4' stem cell markers Bmi1, Tert, Hopx and Lrig1 are robustly expressed in CBC cells.
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