Notch Pathway Regulation of Intestinal Cell Fate

Dempsey, Peter J.; Bohin, Natacha; Samuelson, Linda C.

doi:10.1016/b978-0-12-809954-4.00006-2

Cited by 3 publications

(2 citation statements)

References 476 publications

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“…NOTCH1 and DLL1 are, respectively, the receptor and the ligand that activate the Notch signaling pathway, which regulates stem-cell maintenance and progenitor cell proliferation. Lastly, WNT3A, a member of the WNT family, induces the formation of the heterodimeric complex of Frizzled and LGR5 that, in turn, activates the expression of genes crucial for stem-cell identity, and its gradient controls the transition from proliferating stem cell to transient amplifying cell toward full differentiation [15,24,25].…”

Section: The Intestinal Stem-cell Niche Morphological and Molecular Amentioning

confidence: 99%

The 3D Pattern of the Rainbow Trout (Oncorhynchus mykiss) Enterocytes and Intestinal Stem Cells

Verdile

Pasquariello

Brevini

et al. 2020

IJMS

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We previously showed that, according to the frequency and distribution of specific cell types, the rainbow trout (RT) intestinal mucosa can be divided in two regions that form a complex nonlinear three-dimensional (3D) pattern and have a different renewal rate. This work had two aims. First, we investigated whether the unusual distribution of cell populations reflects a similar distribution of functional activities. To this end, we determined the protein expression pattern of three well-defined enterocytes functional markers: peptide transporter 1 (PepT1), sodium–glucose/galactose transporter 1 (SGLT-1), and fatty-acid-binding protein 2 (Fabp2). Second, we characterized the structure of RT intestinal stem-cell (ISC) niche and determined whether the different proliferative is accompanied by a different organization and/or extension of the stem-cell population. We studied the expression and localization of well-characterized mammal ISC markers: LGR5, HOPX, SOX9, NOTCH1, DLL1, and WNT3A. Our results indicate that morphological similarity is associated with similar function only between the first portion of the mid-intestine and the apical part of the complex folds in the second portion. Mammal ISC markers are all expressed in RT, but their localization is completely different, suggesting also substantial functional differences. Lastly, higher renewal rates are supported by a more abundant ISC population.

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Section: The Intestinal Stem-cell Niche Morphological and Molecular Amentioning

confidence: 99%

The 3D Pattern of the Rainbow Trout (Oncorhynchus mykiss) Enterocytes and Intestinal Stem Cells

Verdile

Pasquariello

Brevini

et al. 2020

IJMS

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“…Wnt/R-spondin and Notch signaling have been identified as the primary niche pathways promoting ISC self-renewal, with pathway disruption leading to CBC loss and crypt collapse. While ISC Wnt signaling is regulated by ligands secreted from both epithelial and stromal cell sources ( Degirmenci et al., 2018 , Farin et al., 2012 , Greicius et al., 2018 , San Roman et al., 2014 , Shoshkes-Carmel et al., 2018 ), Notch signaling in the crypt is likely to be epithelial specific because it requires direct cell-to-cell contact ( Dempsey et al., 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Rapid Crypt Cell Remodeling Regenerates the Intestinal Stem Cell Niche after Notch Inhibition

et al. 2020

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Summary Intestinal crypts have great capacity for repair and regeneration after intestinal stem cell (ISC) injury. Here, we define the cellular remodeling process resulting from ISC niche interruption by transient Notch pathway inhibition in adult mice. Although ISCs were retained, lineage tracing demonstrated a marked reduction in ISC function after Notch disruption. Surprisingly, Notch ligand-expressing Paneth cells were rapidly lost by apoptotic cell death. The ISC-Paneth cell changes were followed by a regenerative response, characterized by expansion of cells expressing Notch ligands Dll1 and Dll4 , enhanced Notch signaling, and a proliferative surge. Lineage tracing and organoid studies showed that Dll1 -expressing cells were activated to function as multipotential progenitors, generating both absorptive and secretory cells and replenishing the vacant Paneth cell pool. Our analysis uncovered a dynamic, multicellular remodeling response to acute Notch inhibition to repair the niche and restore homeostasis. Notably, this crypt regenerative response did not require ISC loss.

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Transcriptional programmes underlying cellular identity and microbial responsiveness in the intestinal epithelium

Heppert

Davison

Kelly

et al. 2020

Nat Rev Gastroenterol Hepatol

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Notch Pathway Regulation of Intestinal Cell Fate

Cited by 3 publications

References 476 publications

The 3D Pattern of the Rainbow Trout (Oncorhynchus mykiss) Enterocytes and Intestinal Stem Cells

The 3D Pattern of the Rainbow Trout (Oncorhynchus mykiss) Enterocytes and Intestinal Stem Cells

Rapid Crypt Cell Remodeling Regenerates the Intestinal Stem Cell Niche after Notch Inhibition

Transcriptional programmes underlying cellular identity and microbial responsiveness in the intestinal epithelium

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