Gene expression patterns of human colon tops and basal crypts and BMP antagonists as intestinal stem cell niche factors.
Cynthia Kosinski,Vivian S. W. Li,Annie S Y Chan,Ji Zhang,Coral Ho,Wai Yin Tsui,Tsun Leung Chan,Randy C. Mifflin,Don W. Powell,Siu Tsan Yuen,Suet Yi Leung,Xin Chen +11 more
TLDR
This study suggests that BMP antagonists are candidate signaling components that make up the intestinal epithelial stem cell niche, and applies gene expression analysis of normal human colon tops and basal crypts to provide a comprehensive picture of human colonic epithelial cell differentiation.Abstract:
Human 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.read more
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The consensus molecular subtypes of colorectal cancer
Justin Guinney,Rodrigo Dienstmann,Rodrigo Dienstmann,Xingwu Wang,Xingwu Wang,Aurélien de Reyniès,Andreas Schlicker,Charlotte Soneson,Laetitia Marisa,Paul Roepman,Gift Nyamundanda,Paolo Angelino,Brian M. Bot,Jeffrey S. Morris,Iris Simon,Sarah Gerster,Evelyn Fessler,Felipe De Sousa E Melo,Edoardo Missiaglia,Hena R. Ramay,David Barras,Krisztian Homicsko,Dipen M. Maru,Ganiraju C. Manyam,Bradley M. Broom,Valérie Boige,Beatriz Perez-Villamil,Ted Laderas,Ramon Salazar,Joe W. Gray,Douglas Hanahan,Josep Tabernero,René Bernards,Stephen H. Friend,Pierre Laurent-Puig,Jan Paul Medema,Anguraj Sadanandam,Lodewyk F. A. Wessels,Mauro Delorenzi,Mauro Delorenzi,Scott Kopetz,Louis Vermeulen,Sabine Tejpar +42 more
TL;DR: An international consortium dedicated to large-scale data sharing and analytics across expert groups is formed, showing marked interconnectivity between six independent classification systems coalescing into four consensus molecular subtypes (CMSs) with distinguishing features.
Journal ArticleDOI
Stem cells, self-renewal, and differentiation in the intestinal epithelium.
TL;DR: In this review, the identification of intestinal stem cells is described and genetic studies that have helped to elucidate those signals important for progenitor cells to differentiate into one of the specialized intestinal epithelial cell types are discussed.
Journal ArticleDOI
Epidemiology of colorectal cancer: incidence, mortality, survival, and risk factors
TL;DR: According to GLOBOCAN 2018 data, colorectal cancer (CRC) is the third most deadly and fourth most commonly diagnosed cancer in the world.
Journal ArticleDOI
Coexistence of Quiescent and Active Adult Stem Cells in Mammals
Linheng Li,Hans Clevers +1 more
TL;DR: It is proposed that quiescent and active stem cell populations have separate but cooperative functional roles in a so-called “zoned” stem cell model.
Journal ArticleDOI
Eph-ephrin bidirectional signaling in physiology and disease.
TL;DR: New findings reveal that Eph receptors and ephrins coordinate not only developmental processes but also the normal physiology and homeostasis of many adult organs, and balance of Eph/ephrin function may contribute to a variety of diseases.
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