scholarly journals Crypt-restricted proliferation and commitment to the Paneth cell lineage following Apc loss in the mouse intestine

Development ◽  
2005 ◽  
Vol 132 (6) ◽  
pp. 1443-1451 ◽  
Author(s):  
P. Andreu
Keyword(s):  
Paneth Cell ◽  
Cell Lineage ◽  
Mouse Intestine

scholarly journals RIP140 Represses Intestinal Paneth Cell Differentiation and Interplays with SOX9 Signaling in Colorectal Cancer

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3192
Author(s):  
Antoine Gleizes ◽  
Mouna Triki ◽  
Sandrine Bonnet ◽  
Naomi Baccari ◽  
Gabriel Jimenez-Dominguez ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Differentiation ◽  
Paneth Cell ◽  
Wnt Signaling Pathway ◽  
Cell Lineage ◽  
Human Colon ◽  
Luciferase Reporter ◽  
Loss Of Function ◽  
Sox9 Expression ◽  
Human Colon Cancer

RIP140 is a major transcriptional coregulator of gut homeostasis and tumorigenesis through the regulation of Wnt/APC signaling. Here, we investigated the effect of RIP140 on Paneth cell differentiation and its interplay with the transcription factor SOX9. Using loss of function mouse models, human colon cancer cells, and tumor microarray data sets we evaluated the role of RIP140 in SOX9 expression and activity using RT-qPCR, immunohistochemistry, luciferase reporter assays, and GST-pull down. We first evidence that RIP140 strongly represses the Paneth cell lineage in the intestinal epithelium cells by inhibiting Sox9 expression. We then demonstrate that RIP140 interacts with SOX9 and inhibits its transcriptional activity. Our results reveal that the Wnt signaling pathway exerts an opposite regulation on SOX9 and RIP140. Finally, the levels of expression of RIP140 and SOX9 exhibit a reverse response and prognosis value in human colorectal cancer biopsies. This work highlights an intimate transcriptional cross-talk between RIP140 and SOX9 in intestinal physiopathology.

scholarly journals PANETH CELL GRANULE OF MOUSE INTESTINE

1962 ◽  
Vol 15 (1) ◽  
pp. 136-139 ◽  
Author(s):  
H. M. Selzman ◽  
Robert A. Liebelt
Keyword(s):  
Paneth Cell ◽  
Cell Granule ◽  
Mouse Intestine

Abnormal Paneth cell granule dissolution and compromised resistance to bacterial colonization in the intestine of CF mice

2004 ◽  
Vol 286 (6) ◽  
pp. G1050-G1058 ◽  
Author(s):  
Lane L. Clarke ◽  
Lara R. Gawenis ◽  
Emily M. Bradford ◽  
Louise M. Judd ◽  
Kathryn T. Boyle ◽  
...  
Keyword(s):  
Northern Blot Analysis ◽  
Clinical Symptoms ◽  
Bacterial Colonization ◽  
Paneth Cell ◽  
Light And Electron Microscopy ◽  
Paneth Cells ◽  
Real Time Quantitative Pcr ◽  
Granule Morphology ◽  
Mouse Intestine ◽  
Osmotic Laxative

Paneth cells of intestinal crypts contribute to host defense by producing antimicrobial peptides that are packaged as granules for secretion into the crypt lumen. Here, we provide evidence using light and electron microscopy that postsecretory Paneth cell granules undergo limited dissolution and accumulate within the intestinal crypts of cystic fibrosis (CF) mice. On the basis of this finding, we evaluated bacterial colonization and expression of two major constituents of Paneth cells, i.e., α-defensins (cryptdins) and lysozyme, in CF murine intestine. Paneth cell granules accumulated in intestinal crypt lumens in both untreated CF mice with impending intestinal obstruction and in CF mice treated with an osmotic laxative that prevented overt clinical symptoms and mucus accretion. Ultrastructure studies indicated little change in granule morphology within mucus casts, whereas granules in laxative-treated mice appear to undergo limited dissolution. Protein extracts from CF intestine had increased levels of processed cryptdins compared with those from wild-type (WT) littermates. Nonetheless, colonization with aerobic bacteria species was not diminished in the CF intestine and oral challenge with a cryptdin-sensitive enteric pathogen, Salmonella typhimurium, resulted in greater colonization of CF compared with WT intestine. Modest downregulation of cryptdin and lysozyme mRNA in CF intestine was shown by microarray analysis, real-time quantitative PCR, and Northern blot analysis. Based on these findings, we conclude that antimicrobial peptide activity in CF mouse intestine is compromised by inadequate dissolution of Paneth cell granules within the crypt lumens.

scholarly journals Intestinal Neurod1 expression impairs paneth cell differentiation and promotes enteroendocrine lineage specification

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Hui Joyce Li ◽  
Subir K. Ray ◽  
Ning Pan ◽  
Jody Haigh ◽  
Bernd Fritzsch ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Epithelial Cells ◽  
Cell Fate ◽  
Intestinal Epithelial Cells ◽  
Paneth Cell ◽  
Substantial Reduction ◽  
Ectopic Expression ◽  
Cell Lineage ◽  
Intestinal Epithelial ◽  
Conditional Expression

AbstractTranscription factor Neurod1 is required for enteroendocrine progenitor differentiation and maturation. Several earlier studies indicated that ectopic expression of Neurod1 converted non- neuronal cells into neurons. However, the functional consequence of ectopic Neurod1 expression has not been examined in the GI tract, and it is not known whether Neurod1 can similarly switch cell fates in the intestine. We generated a mouse line that would enable us to conditionally express Neurod1 in intestinal epithelial cells at different stages of differentiation. Forced expression of Neurod1 throughout intestinal epithelium increased the number of EECs as well as the expression of EE specific transcription factors and hormones. Furthermore, we observed a substantial reduction of Paneth cell marker expression, although the expressions of enterocyte-, tuft- and goblet-cell specific markers are largely not affected. Our earlier study indicated that Neurog3+ progenitor cells give rise to not only EECs but also Goblet and Paneth cells. Here we show that the conditional expression of Neurod1 restricts Neurog3+ progenitors to adopt Paneth cell fate, and promotes more pronounced EE cell differentiation, while such effects are not seen in more differentiated Neurod1+ cells. Together, our data suggest that forced expression of Neurod1 programs intestinal epithelial cells more towards an EE cell fate at the expense of the Paneth cell lineage and the effect ceases as cells mature to EE cells.

scholarly journals Fibroblast growth factor receptor-3 regulates Paneth cell lineage allocation and accrual of epithelial stem cells during murine intestinal development

2009 ◽  
Vol 297 (1) ◽  
pp. G168-G178 ◽  
Author(s):  
Alda Vidrich ◽  
Jenny M. Buzan ◽  
Brooks Brodrick ◽  
Chibuzo Ilo ◽  
Leigh Bradley ◽  
...  
Keyword(s):  
Stem Cells ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor Receptor ◽  
Paneth Cell ◽  
Cell Lineage ◽  
Growth Factor Receptor ◽  
Intestinal Development ◽  
Fibroblast Growth ◽  
Epithelial Stem Cells

Fibroblast growth factor receptor 3 (FGFR-3) is expressed in the lower crypt epithelium, where stem cells of the intestine reside. The role of FGFR-3 signaling in regulating features of intestinal morphogenesis was examined in FGFR-3-null (FGFR-3−/−) mice. FGFR-3−/− mice had only about half the number of intestinal crypts and a marked decrease in the number of functional clonogenic stem cells, as assessed by an in vivo microcolony-forming assay, compared with wild-type littermates. A marked deficit in allocation of progenitor cells to Paneth cell differentiation was noted, although all the principal epithelial lineages were represented in FGFR-3−/− mice. The total cellular content and nuclear localization of β-catenin protein were reduced in FGFR-3−/− mice, as was expression of cyclin D1 and matrix metalloproteinase-7, major downstream targets of β-catenin/T cell factor-4 (Tcf-4) signaling. Activation of FGFR-3 in Caco-2 cells, an intestinal epithelial cell line, abrogated the fall in β-catenin/Tcf-4 signaling activity that is normally observed in these cells as cultures become progressively more confluent. These findings are consistent with the hypothesis that, during intestinal development, FGFR-3 signaling regulates crypt epithelial stem cell expansion and crypt morphogenesis, as well as Paneth cell lineage specification, through β-catenin/Tcf-4-dependent and -independent pathways.

scholarly journals Detection of CD1 mRNA in Paneth cells of the mouse intestine by in situ hybridization.

1992 ◽  
Vol 40 (10) ◽  
pp. 1527-1534 ◽  
Author(s):  
J Lacasse ◽  
L H Martin
Keyword(s):  
In Situ Hybridization ◽  
Cell Biology ◽  
Paneth Cell ◽  
Intestinal Flora ◽  
Intraepithelial Lymphocytes ◽  
Paneth Cells ◽  
Peripheral T Cells ◽  
Mouse Intestine ◽  
Cluster Of Differentiation

Cluster of differentiation 1 (CD1) antigens are a family of non-MHC but Class I-like molecules that have been identified in humans and rodents. Although their function(s) remains unknown, it has been proposed that CD1 may present antigens to specific subsets of peripheral T-cells. We now provide evidence in support of this hypothesis through the demonstration by in situ hybridization that Paneth cells of the mouse intestine express CD1 mRNA. These cells are thought to be involved in the immunological regulation of intestinal flora and could accomplish this task through interactions with intestinal intraepithelial lymphocytes. The expression and localization of CD1 mRNA was confirmed by both autoradiographic and non-isotopic techniques. The relevance of these results to CD1 function as well as to Paneth cell biology is discussed.

scholarly journals Constitutive STAT5 activation regulates Paneth and Paneth-like cells to control Clostridium difficile colitis

2019 ◽  
Vol 2 (2) ◽  
pp. e201900296 ◽  
Author(s):  
Ruixue Liu ◽  
Richard Moriggl ◽  
Dongsheng Zhang ◽  
Haifeng Li ◽  
Rebekah Karns ◽  
...  
Keyword(s):  
Clostridium Difficile ◽  
Cell Fate ◽  
Intestinal Inflammation ◽  
Paneth Cell ◽  
Cell Lineage ◽  
Niche Differentiation ◽  
Paneth Cells ◽  
Lineage Tracing ◽  
Intestinal Epithelial ◽  
Clostridium Difficile Colitis

Clostridium difficile impairs Paneth cells, driving intestinal inflammation that exaggerates colitis. Besides secreting bactericidal products to restrain C. difficile, Paneth cells act as guardians that constitute a niche for intestinal epithelial stem cell (IESC) regeneration. However, how IESCs are sustained to specify Paneth-like cells as their niche remains unclear. Cytokine-JAK-STATs are required for IESC regeneration. We investigated how constitutive STAT5 activation (Ca-pYSTAT5) restricts IESC differentiation towards niche cells to restrain C. difficile infection. We generated inducible transgenic mice and organoids to determine the effects of Ca-pYSTAT5-induced IESC lineages on C. difficile colitis. We found that STAT5 absence reduced Paneth cells and predisposed mice to C. difficile ileocolitis. In contrast, Ca-pYSTAT5 enhanced Paneth cell lineage tracing and restricted Lgr5 IESC differentiation towards pYSTAT5+Lgr5−CD24+Lyso+ or cKit+ niche cells, which imprinted Lgr5hiKi67+ IESCs. Mechanistically, pYSTAT5 activated Wnt/β-catenin signaling to determine Paneth cell fate. In conclusion, Ca-pYSTAT5 gradients control niche differentiation. Lack of pYSTAT5 reduces the niche cells to sustain IESC regeneration and induces C. difficile ileocolitis. STAT5 may be a transcription factor that regulates Paneth cells to maintain niche regeneration.

scholarly journals Non-canonical Wnt/PCP signalling regulates intestinal stem cell lineage priming towards enteroendocrine and Paneth cell fates

2021 ◽  
Vol 23 (1) ◽  
pp. 23-31
Author(s):  
Anika Böttcher ◽  
Maren Büttner ◽  
Sophie Tritschler ◽  
Michael Sterr ◽  
Alexandra Aliluev ◽  
...  
Keyword(s):  
Stem Cell ◽  
Paneth Cell ◽  
Cell Lineage ◽  
Intestinal Stem Cell ◽  
Cell Fates ◽  
Stem Cell Lineage ◽  
Lineage Priming ◽  
Canonical Wnt
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