PMID- 22692129
OWN - NLM
STAT- MEDLINE
DCOM- 20120924
LR  - 20240210
IS  - 1460-2075 (Electronic)
IS  - 0261-4189 (Print)
IS  - 0261-4189 (Linking)
VI  - 31
IP  - 14
DP  - 2012 Jun 12
TI  - The Lgr5 intestinal stem cell signature: robust expression of proposed quiescent 
      '+4' cell markers.
PG  - 3079-91
LID - 10.1038/emboj.2012.166 [doi]
AB  - 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.
FAU - Munoz, Javier
AU  - Munoz J
AD  - Bijvoet Center for Biomolecular Research, Utrecht Institute for Pharmaceutical 
      Sciences, University, The Netherlands.
FAU - Stange, Daniel E
AU  - Stange DE
FAU - Schepers, Arnout G
AU  - Schepers AG
FAU - van de Wetering, Marc
AU  - van de Wetering M
FAU - Koo, Bon-Kyoung
AU  - Koo BK
FAU - Itzkovitz, Shalev
AU  - Itzkovitz S
FAU - Volckmann, Richard
AU  - Volckmann R
FAU - Kung, Kevin S
AU  - Kung KS
FAU - Koster, Jan
AU  - Koster J
FAU - Radulescu, Sorina
AU  - Radulescu S
FAU - Myant, Kevin
AU  - Myant K
FAU - Versteeg, Rogier
AU  - Versteeg R
FAU - Sansom, Owen J
AU  - Sansom OJ
FAU - van Es, Johan H
AU  - van Es JH
FAU - Barker, Nick
AU  - Barker N
FAU - van Oudenaarden, Alexander
AU  - van Oudenaarden A
FAU - Mohammed, Shabaz
AU  - Mohammed S
FAU - Heck, Albert J R
AU  - Heck AJ
FAU - Clevers, Hans
AU  - Clevers H
LA  - eng
GR  - 12481/CRUK_/Cancer Research UK/United Kingdom
GR  - U54 CA143874/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120612
PL  - England
TA  - EMBO J
JT  - The EMBO journal
JID - 8208664
RN  - 0 (Antigens, Differentiation)
RN  - 0 (Calcium-Binding Proteins)
RN  - 0 (Lgr5 protein, mouse)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - 0 (SMOC-2 protein, mouse)
SB  - IM
MH  - Animals
MH  - Antigens, Differentiation/genetics/*metabolism
MH  - Calcium-Binding Proteins/genetics/metabolism
MH  - Gene Expression Profiling
MH  - *Gene Expression Regulation
MH  - Intestinal Mucosa/*metabolism
MH  - Intestines/cytology
MH  - Mice
MH  - Mice, Transgenic
MH  - Oligonucleotide Array Sequence Analysis
MH  - RNA, Messenger/biosynthesis/genetics
MH  - Receptors, G-Protein-Coupled/genetics/*metabolism
MH  - Stem Cells/cytology/*metabolism
PMC - PMC3400017
COIS- The authors declare that they have no conflict of interest.
EDAT- 2012/06/14 06:00
MHDA- 2012/09/25 06:00
PMCR- 2013/07/18
CRDT- 2012/06/14 06:00
PHST- 2012/03/20 00:00 [received]
PHST- 2012/05/15 00:00 [accepted]
PHST- 2012/06/14 06:00 [entrez]
PHST- 2012/06/14 06:00 [pubmed]
PHST- 2012/09/25 06:00 [medline]
PHST- 2013/07/18 00:00 [pmc-release]
AID - emboj2012166 [pii]
AID - 10.1038/emboj.2012.166 [doi]
PST - epublish
SO  - EMBO J. 2012 Jun 12;31(14):3079-91. doi: 10.1038/emboj.2012.166.