Wnt pathway regulation of intestinal stem cells

Mah, Amanda T.; Yan, Kelley S.; Kuo, Calvin J.

doi:10.1113/jp271754

Cited by 124 publications

(102 citation statements)

References 86 publications

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“…ISCs require the Wnt signal for its self-renewal and differentiation; however, an uncontrolled Wnt pathway leads to the expansion of stem or progenitor cells and aberrant lineage decisions (23,36). Several studies have linked H3K36 methylation to abnormal differentiation or proliferation.…”

Section: Discussionmentioning

confidence: 99%

Histone methyltransferase SETD2 modulates alternative splicing to inhibit intestinal tumorigenesis

Yuan¹,

Ni²,

Fu³

et al. 2017

Journal of Clinical Investigation

138

119

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Section: Discussionmentioning

confidence: 99%

Histone methyltransferase SETD2 modulates alternative splicing to inhibit intestinal tumorigenesis

Yuan¹,

Ni²,

Fu³

et al. 2017

Journal of Clinical Investigation

138

119

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“…We report that Wnt-associated genes are downregulated (Figures 4 and 11). That the TA and ISC populations differentially respond to Wnt signals is not unprecedented, because it is known that discrete ISC populations, as well as downstream progenitor cells, respond to different proliferative signaling cues 78 . For example, Wnt signaling targets the active-cycling ISC population because nuclear β-catenin is found in these cells, yet nuclear β-catenin is absent in the TA zone (Figure 11 A ).…”

Section: Discussionmentioning

confidence: 99%

Cell Adhesion Molecule CD166/ALCAM Functions Within the Crypt to Orchestrate Murine Intestinal Stem Cell Homeostasis

Smith

Davies

Levin

et al. 2017

Cellular and Molecular Gastroenterology and Hepatology

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Background & AimsIntestinal epithelial homeostasis is maintained by active-cycling and slow-cycling stem cells confined within an instructive crypt-based niche. Exquisite regulating of these stem cell populations along the proliferation-to-differentiation axis maintains a homeostatic balance to prevent hyperproliferation and cancer. Although recent studies focus on how secreted ligands from mesenchymal and epithelial populations regulate intestinal stem cells (ISCs), it remains unclear what role cell adhesion plays in shaping the regulatory niche. Previously we have shown that the cell adhesion molecule and cancer stem cell marker, CD166/ALCAM (activated leukocyte cell adhesion molecule), is highly expressed by both active-cycling Lgr5+ ISCs and adjacent Paneth cells within the crypt base, supporting the hypothesis that CD166 functions to mediate ISC maintenance and signal coordination.MethodsHere we tested this hypothesis by analyzing a CD166–/– mouse combined with immunohistochemical, flow cytometry, gene expression, and enteroid culture.ResultsWe found that animals lacking CD166 expression harbored fewer active-cycling Lgr5+ ISCs. Homeostasis was maintained by expansion of the transit-amplifying compartment and not by slow-cycling Bmi1+ ISC stimulation. Loss of active-cycling ISCs was coupled with deregulated Paneth cell homeostasis, manifested as increased numbers of immature Paneth progenitors due to decreased terminal differentiation, linked to defective Wnt signaling. CD166–/– Paneth cells expressed reduced Wnt3 ligand expression and depleted nuclear β-catenin.ConclusionsThese data support a function for CD166 as an important cell adhesion molecule that shapes the signaling microenvironment by mediating ISC–niche cell interactions. Furthermore, loss of CD166 expression results in decreased ISC and Paneth cell homeostasis and an altered Wnt microenvironment.

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“…Two major signaling pathways that are important for intestinal proliferation in the late neonatal and adult intestine are the Wnt/β-catenin and Notch signaling pathways [106,127–134]. For detailed reviews on Wnt and Notch signaling in the intestinal stem cell, see: [135,136]. Although proliferation in the pre-villus intestinal epithelium in mice can occur in the absence of Wnt/β-catenin signaling, once villi form at E15.5, proliferation is dependent on Wnt/β-catenin signaling.…”

Section: Development and Maturation Of The Intestine Following Villusmentioning

confidence: 99%

Morphogenesis and maturation of the embryonic and postnatal intestine

Chin

Hill

Aurora

et al. 2017

Seminars in Cell & Developmental Biology

174

129

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The intestine is a vital organ responsible for nutrient absorption, bile and waste excretion, and a major site of host immunity. In order to keep up with daily demands, the intestine has evolved a mechanism to expand the absorptive surface area by undergoing a morphogenetic process to generate finger-like units called villi. These villi house specialized cell types critical for both absorbing nutrients from food, and for protecting the host from commensal and pathogenic microbes present in the adult gut. In this review, we will discuss mechanisms that coordinate intestinal development, growth, and maturation of the small intestine, starting from the formation of the early gut tube, through villus morphogenesis and into early postnatal life when the intestine must adapt to the acquisition of nutrients through food intake, and to interactions with microbes.

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Wnt pathway regulation of intestinal stem cells

Cited by 124 publications

References 86 publications

Histone methyltransferase SETD2 modulates alternative splicing to inhibit intestinal tumorigenesis

Histone methyltransferase SETD2 modulates alternative splicing to inhibit intestinal tumorigenesis

Cell Adhesion Molecule CD166/ALCAM Functions Within the Crypt to Orchestrate Murine Intestinal Stem Cell Homeostasis

Morphogenesis and maturation of the embryonic and postnatal intestine

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