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Article: Gene expression patterns of human colon tops and basal crypts and BMP antagonists as intestinal stem cell niche factors

TitleGene expression patterns of human colon tops and basal crypts and BMP antagonists as intestinal stem cell niche factors
Authors
Issue Date2007
PublisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.org
Citation
Proceedings Of The National Academy Of Sciences Of The United States Of America, 2007, v. 104 n. 39, p. 15418-15423 How to Cite?
AbstractHuman colonic epithelial cell renewal, proliferation, and differentiation are stringently controlled by numerous regulatory pathways. To identify genetic programs of human colonic epithelial cell differentiation in vivo as well as candidate marker genes that define colonic epithelial stem/progenitor cells and the stem cell niche, we applied gene expression analysis of normal human colon tops and basal crypts by using expression microarrays with 30,000 genes. Nine hundred and sixty-nine cDNA clones were found to be differentially expressed between human colon crypts and tops. Pathway analysis revealed the differential expression of genes involved in cell cycle maintenance and apoptosis, as well as genes in bone morphogenetic protein (BMP), Notch, Wnt, EPH, and MYC signaling pathways. BMP antagonists gremlin 1, gremlin 2, and chordin-like 1 were found to be expressed by colon crypts. In situ hybridization and RT-PCR confirmed that these BMP antagonists are expressed by intestinal cryptal myofibroblasts and smooth muscle cells at the colon crypt. In vitro analysis demonstrated that gremlin 1 partially inhibits Caco-2 cell differentiation upon confluence and activates Wnt signaling in normal rat intestinal epithelial cells. Collectively, the expression data set provides a comprehensive picture of human colonic epithelial cell differentiation. Our study also suggests that BMP antagonists are candidate signaling components that make up the intestinal epithelial stem cell niche. © 2007 by The National Academy of Sciences of the USA.
Persistent Identifierhttp://hdl.handle.net/10722/88560
ISSN
2015 Impact Factor: 9.423
2015 SCImago Journal Rankings: 6.883
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorKosinski, Cen_HK
dc.contributor.authorLi, VSWen_HK
dc.contributor.authorChan, ASYen_HK
dc.contributor.authorZhang, Jen_HK
dc.contributor.authorHo, Cen_HK
dc.contributor.authorWai, YTen_HK
dc.contributor.authorTsun, LCen_HK
dc.contributor.authorMifflin, RCen_HK
dc.contributor.authorPowell, DWen_HK
dc.contributor.authorSiu, TYen_HK
dc.contributor.authorSuet, YLen_HK
dc.contributor.authorChen, Xen_HK
dc.date.accessioned2010-09-06T09:44:58Z-
dc.date.available2010-09-06T09:44:58Z-
dc.date.issued2007en_HK
dc.identifier.citationProceedings Of The National Academy Of Sciences Of The United States Of America, 2007, v. 104 n. 39, p. 15418-15423en_HK
dc.identifier.issn0027-8424en_HK
dc.identifier.urihttp://hdl.handle.net/10722/88560-
dc.description.abstractHuman colonic epithelial cell renewal, proliferation, and differentiation are stringently controlled by numerous regulatory pathways. To identify genetic programs of human colonic epithelial cell differentiation in vivo as well as candidate marker genes that define colonic epithelial stem/progenitor cells and the stem cell niche, we applied gene expression analysis of normal human colon tops and basal crypts by using expression microarrays with 30,000 genes. Nine hundred and sixty-nine cDNA clones were found to be differentially expressed between human colon crypts and tops. Pathway analysis revealed the differential expression of genes involved in cell cycle maintenance and apoptosis, as well as genes in bone morphogenetic protein (BMP), Notch, Wnt, EPH, and MYC signaling pathways. BMP antagonists gremlin 1, gremlin 2, and chordin-like 1 were found to be expressed by colon crypts. In situ hybridization and RT-PCR confirmed that these BMP antagonists are expressed by intestinal cryptal myofibroblasts and smooth muscle cells at the colon crypt. In vitro analysis demonstrated that gremlin 1 partially inhibits Caco-2 cell differentiation upon confluence and activates Wnt signaling in normal rat intestinal epithelial cells. Collectively, the expression data set provides a comprehensive picture of human colonic epithelial cell differentiation. Our study also suggests that BMP antagonists are candidate signaling components that make up the intestinal epithelial stem cell niche. © 2007 by The National Academy of Sciences of the USA.en_HK
dc.languageengen_HK
dc.publisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.orgen_HK
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of Americaen_HK
dc.rightsProceedings of the National Academy of Sciences. Copyright © National Academy of Sciences.en_HK
dc.subject.meshApoptosisen_HK
dc.subject.meshBone Morphogenetic Proteins - metabolismen_HK
dc.subject.meshCaco-2 Cellsen_HK
dc.subject.meshColon - metabolismen_HK
dc.subject.meshEpithelial Cells - metabolismen_HK
dc.subject.meshEye Proteins - biosynthesisen_HK
dc.subject.meshGene Expression Profilingen_HK
dc.subject.meshGene Expression Regulationen_HK
dc.subject.meshHumansen_HK
dc.subject.meshIntercellular Signaling Peptides and Proteins - biosynthesisen_HK
dc.subject.meshIntestines - metabolismen_HK
dc.subject.meshNerve Tissue Proteins - biosynthesisen_HK
dc.subject.meshReceptors, Notch - metabolismen_HK
dc.subject.meshSignal Transductionen_HK
dc.subject.meshStem Cells - metabolismen_HK
dc.titleGene expression patterns of human colon tops and basal crypts and BMP antagonists as intestinal stem cell niche factorsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0027-8424&volume=104&issue=39&spage=15418&epage=23&date=2007&atitle=Gene+expression+patterns+of+human+colon+tops+and+basal+crypts+and+BMP+antagonists+as+intestinal+stem+cell+niche+factorsen_HK
dc.identifier.emailTsun, LC:tlchan@hku.hken_HK
dc.identifier.emailSuet, YL:suetyi@hkucc.hku.hken_HK
dc.identifier.authorityTsun, LC=rp00418en_HK
dc.identifier.authoritySuet, YL=rp00359en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1073/pnas.0707210104en_HK
dc.identifier.pmid17881565-
dc.identifier.scopuseid_2-s2.0-34848868159en_HK
dc.identifier.hkuros138343en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-34848868159&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume104en_HK
dc.identifier.issue39en_HK
dc.identifier.spage15418en_HK
dc.identifier.epage15423en_HK
dc.identifier.isiWOS:000249806900045-
dc.publisher.placeUnited Statesen_HK
dc.identifier.citeulike3187075-

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