Journal article
The Lgr5 intestinal stem cell signature: robust expression of proposed quiescent '+4' cell markers
EMBO Journal, Vol.31(14), pp.3079-3091
Jul/2012
Abstract
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. The EMBO Journal (2012) 31, 3079-3091. doi:10.1038/emboj.2012.166; Published online 12 June 2012
Details
- Title
- The Lgr5 intestinal stem cell signature; robust expression of proposed quiescent '+4' cell markers
- Creators
- de Wetering, Marc van de Wetering (null)Bon-Kyoung Koo (null)Shalev Itzkovitz (null) - 972WIS_INST___122Richard Volckmann (null)Kevin S. Kung (null)Jan Koster (null)Sorina Radulescu (null)Kevin Myant (null)Rogier Versteeg (null)Owen J. Sansom (null)Es, Johan H. van Es (null)Nick Barker (null)Oudenaarden, Alexander van Oudenaarden (null)Shabaz Mohammed (null)Albert J. R. Heck (null)Hans Clevers (null)
- Resource Type
- Journal article
- Publication Details
- EMBO Journal, Vol.31(14), pp.3079-3091; Jul/2012
- Number of pages
- 13
- Language
- English
- DOI
- https://doi.org/10.1038/emboj.2012.166
- Grant note
- CBG; Ti Pharma [T3-106]; EU/Health [F4-2007-200720]; ERC [232814]; Cancer Research UK; NIH/NCI Physical Sciences Oncology Center at MIT [U54CA143874] We thank Harm Post and Marco Hennrich for technical support on the SCX and Maaike van den Born as well as Harry Begthel for histological support. DES is supported by a grant from CBG; AGS and JvE by a grant from Ti Pharma/T3-106; MvdW by a grant from EU/Health F4-2007-200720; B-KK by a grant from Advanced ERC 232814. OJS, KM and SR are funded by a Cancer Research UK core grant; AvO, SI and KSK are supported by the NIH/NCI Physical Sciences Oncology Center at MIT (U54CA143874)._ALMAME_DELIMITER_
- Record Identifier
- 993262432703596
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