Gene expression profiling of intestinal epithelial cell maturation along the crypt-villus axis

Mariadason, John M.; Nicholas, Courtney; L’Italien, Kaitlin E.; Zhuang, Min; Smartt, Helena J.M.; Heerdt, Barbara G.; Yang, Wancai; Corner, Georgia; Wilson, Andrew J.; Klampfer, Lidija; Arango, Diego; Augenlicht, Leonard H.

doi:10.1053/j.gastro.2005.01.054

Cited by 173 publications

(178 citation statements)

References 34 publications

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“…Unsupervised clustering of the data for the 35,112 probe sets that passed initial filtering for all analyses yielded two main branches with 22 of 23 villus samples (F1) in branch A and 24 of 24 crypt samples (F10) in branch B (Fig. S1); this observation was consistent with the expectation and our previously reported data (17,18) that villus cells are highly reprogrammed relative to crypt cells and that the method of cell isolation (Methods and Fig. S7) yields cell fractions highly enriched for each compartment.…”

Section: Resultssupporting

confidence: 90%

Paneth cell marker expression in intestinal villi and colon crypts characterizes dietary induced risk for mouse sporadic intestinal cancer

Wang

Peregrina

Dhima

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Nutritional and genetic risk factors for intestinal tumors are additive on mouse tumor phenotype, establishing that diet and genetic factors impact risk by distinct combinatorial mechanisms. In a mouse model of dietary-induced sporadic small and large intestinal cancer in WT mice in which tumor etiology, lag, incidence, and frequency reflect >90% of intestinal cancer in Western societies, dietary-induced risk altered gene expression profiles predominantly in villus cells of the histologically normal mucosa, in contrast to targeting of crypt cells by inheritance of an Apc 1638N allele or homozygous inactivation of p21 Waf1/cip1 , and profiles induced by each risk factor were distinct at the gene or functional group level. The dietary-induced changes in villus cells encompassed ectopic expression of Paneth cell markers (a lineage normally confined to the bottom of small intestinal crypts), elevated expression of the Wnt receptor Fzd5 and of EphB2 (genes necessary for Paneth cell differentiation and localization to the crypt bottom), and increased Wnt signaling in villus cells. Ectopic elevation of these markers was also present in the colon crypts, which are also sites of sporadic tumors in the nutritional model. Elevating dietary vitamin D 3 and calcium, which prevents tumor development, abrogated these changes in the villus and colon cells. Thus, common intestinal cancer driven by diet involves mechanisms of tumor development distinct from those mechanisms that cause tumors induced by the rare inheritance of a mutant adenomatous polyposis coli (Apc) allele. This is fundamental for understanding how common sporadic tumors arise and in evaluating relative risk in the population.sporadic | colon cancer | Western diet | microarray

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Section: Resultssupporting

confidence: 90%

Paneth cell marker expression in intestinal villi and colon crypts characterizes dietary induced risk for mouse sporadic intestinal cancer

Wang

Peregrina

Dhima

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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“…Moreover, our observation that FZD7 expression is confined to proliferative areas of carcinomas is in agreement with the recent demonstration that FZD7 mRNA is detected only in the proliferative compartment of both small intestine (Gregorieff et al, 2005;Mariadason et al, 2005) and colonic crypts (Gregorieff et al, 2005). Given that Wnt and FZD govern morphogenetic developmental processes, we proposed they have a similar tissue-remodelling function in cancer (Vincan, 2004).…”

Section: Discussionsupporting

confidence: 92%

Frizzled-7 dictates three-dimensional organization of colorectal cancer cell carcinoids

et al. 2006

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Progression of colorectal cancer (CRC) involves spatial and temporal occurrences of epithelial-mesenchymal transition (EMT), whereby tumour cells acquire a more invasive and metastatic phenotype. Subsequently, the disseminated mesenchymal tumour cells must undergo a reverse transition (mesenchymal-epithelial transition, MET) at the site of metastases, as most metastases recapitulate the pathology of their corresponding primary tumours. Importantly, initiation of tumour growth at the secondary site is the rate-limiting step in metastasis. However, investigation of this dynamic reversible EMT and MET that underpins CRC morphogenesis has been hindered by a lack of suitable in vitro models. To this end, we have established a unique in vitro model of CRC morphogenesis, which we term LIM1863-Mph (morphogenetic). LIM1863-Mph cells spontaneously undergo cyclic transitions between two-dimensional monolayer (migratory, mesenchymal) and three-dimensional sphere (carcinoid, epithelial) states. Using RNAi, we demonstrate that FZD7 is necessary for MET of the monolayer cells as loss of FZD7 results in the persistence of a mesenchymal state (increased SNAI2/decreased E-cadherin). Moreover, FZD7 is also required for migration of the LIM1863-Mph monolayer cells. During development, FZD7 orchestrates either migratory or epithelialization events depending on the context. Our findings strongly implicate similar functional diversity for FZD7 during CRC morphogenesis.

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“…Our results reveal alteration in a diverse spectrum of genes reflecting not only a difference in cell proliferation versus differentiation/apoptosis along the colon crypt axis but also changes in various components of key signaling pathways regulating colon stem cell renewal. Although many similarities were noted in comparison with an expression profiling database derived from mouse small intestine (8), our data extend the findings to humans and provide unique information about the colon, including elements highly relevant to colon carcinogenesis. Specifically, our data captured information not only from the epithelial cells, but also the supporting tissue microenvironment, which may contribute critical elements for creating and maintaining the stem cell niche.…”

Section: Discussionsupporting

confidence: 68%

“…Several genomic studies have been applied to study mouse intestinal epithelial stem cells and their differentiation program by using either expression array technology or cDNA library sequencing (7)(8)(9). These gene expression analyses have provided valuable information and candidate markers for mouse gastrointestinal stem/progenitor cells, as well as revealing the differentiation program of these cells.…”

mentioning

confidence: 99%

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

Kosinski

Chan

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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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.gremlin ͉ expression profiling ͉ microarray ͉ crypt maturation program ͉ myofibroblast

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Gene expression profiling of intestinal epithelial cell maturation along the crypt-villus axis

Cited by 173 publications

References 34 publications

Paneth cell marker expression in intestinal villi and colon crypts characterizes dietary induced risk for mouse sporadic intestinal cancer

Paneth cell marker expression in intestinal villi and colon crypts characterizes dietary induced risk for mouse sporadic intestinal cancer

Frizzled-7 dictates three-dimensional organization of colorectal cancer cell carcinoids

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

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