Intestinal Stem Cell Niche: The Extracellular Matrix and Cellular Components

The intestinal epithelium comprises a monolayer of polarised columnar cells organised along the crypt-villus axis. Intestinal stem cells reside at the base of crypts and are constantly nourished by their surrounding niche for maintenance, self-renewal, and differentiation. The cellular microenvironment including the adjacent Paneth cells, stromal cells, smooth muscle cells, and neural cells as well as the extracellular matrix together constitute the intestinal stem cell niche. A dynamic regulatory network exists among the epithelium, stromal cells, and the matrix via complex signal transduction to maintain tissue homeostasis. Dysregulation of these biological or mechanical signals could potentially lead to intestinal injury and disease. In this review, we discuss the role of different intestinal stem cell niche components and dissect the interaction between dynamic matrix factors and regulatory signalling during intestinal stem cell homeostasis.

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Map3k2-Regulated Intestinal Stromal Cells (MRISC) Define a Distinct Sub-cryptic Stem Cell Niche for Damage Induced Wnt Agonist R-spondin1 Production

10.1101/723221 ◽

2019 ◽

Author(s):

Ningbo Wu ◽

Hongxiang Sun ◽

Xiaoyun Zhao ◽

Lei Chen ◽

Yuanyuan Qi ◽

...

Keyword(s):

Stem Cell ◽

Signaling Pathway ◽

Stromal Cells ◽

Stem Cell Niche ◽

Molecular Mechanisms ◽

Intestinal Stem Cell ◽

List Type ◽

Intestinal Damage ◽

Specific Function ◽

Cell Niche

SummaryIntestinal stem cell propagation and differentiation are essential for rapid repair of tissue damage in the gut. While intestinal stromal cells were recently identified as key mediators of this process, the cellular and molecular mechanisms by which this diverse population induces tissue repair remains poorly understood. Here we show that Map3k2 has a colon stromal cell specific function critically required for maintenance of Lgr5+ intestinal stem cells and protection against acute intestinal damage. This Map3k2-specific function is mediated by enhancing Wnt agonist R-spondin1 production. We further reveal a unique novel cell population, named Map3k2-regulated intestinal stromal cells (MRISC), as the primary cellular source of R-spondin1 following intestinal injury. Together, our data identify a novel intestinal stem cell niche organized by MRISC, which specifically dependent on the Map3k2-signaling pathway to augment the production of Wnt agonist R-spondin1 and promote regeneration of the acutely damaged intestine.HighlightsMap3k2 protects mice from DSS-induced colitis by promoting intestinal stem cell regeneration.Map3k2-MAPK pathway cross-talks with Wnt signaling pathway via upregulation of R-spondin1.Map3k2-Regulated Intestinal Stromal Cells (MRISC) marked by co-expression of CD90, CD34 and CD81 defines a novel colonic stem cell niche.

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Abstract 1501: Direct interaction between human pancreatic cancer stem cells and stromal cells remodels extracellular matrix formation for cancer stem cell niche

10.1158/1538-7445.am2012-1501 ◽

2012 ◽

Author(s):

Yuichi Hori ◽

Kazuya Shimizu ◽

Sachie Chiba

Keyword(s):

Pancreatic Cancer ◽

Stem Cells ◽

Extracellular Matrix ◽

Stem Cell ◽

Stromal Cells ◽

Stem Cell Niche ◽

Direct Interaction ◽

Human Pancreatic Cancer ◽

Cell Niche ◽

Pancreatic Cancer Stem Cells

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Faculty Opinions recommendation of Visualization of a short-range Wnt gradient in the intestinal stem-cell niche.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.726134575.793554531 ◽

2018 ◽

Author(s):

Mirna Perez-Moreno

Keyword(s):

Stem Cell ◽

Stem Cell Niche ◽

Short Range ◽

Intestinal Stem Cell ◽

Cell Niche

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Tu1731 Survivin Controls the Homeostasis of the Intestinal Stem Cell Niche

Gastroenterology ◽

10.1016/s0016-5085(13)63095-4 ◽

2013 ◽

Vol 144 (5) ◽

pp. S-833

Author(s):

Eva Martini ◽

Nadine Wittkopf ◽

Claudia Günther ◽

Hitoshi Okada ◽

Markus FF Neurath ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Niche ◽

Intestinal Stem Cell ◽

Cell Niche

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Extracellular matrix and the neural stem cell niche

Developmental Neurobiology ◽

10.1002/dneu.20970 ◽

2011 ◽

Vol 71 (11) ◽

pp. 1006-1017 ◽

Cited By ~ 73

Author(s):

Ilias Kazanis ◽

Charles ffrench-Constant

Keyword(s):

Extracellular Matrix ◽

Stem Cell ◽

Neural Stem Cell ◽

Stem Cell Niche ◽

Neural Stem Cell Niche ◽

Cell Niche

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Erratum: The HSP90 inhibitor, 17AAG, protects the intestinal stem cell niche and inhibits graft versus host disease development

Oncogene ◽

10.1038/onc.2016.63 ◽

2016 ◽

Vol 35 (22) ◽

pp. 2948-2948 ◽

Cited By ~ 2

Author(s):

A-L Joly ◽

A Deepti ◽

A Seignez ◽

A Goloudina ◽

S Hebrard ◽

...

Keyword(s):

Stem Cell ◽

Graft Versus Host Disease ◽

Stem Cell Niche ◽

Hsp90 Inhibitor ◽

Intestinal Stem Cell ◽

Disease Development ◽

Host Disease ◽

Graft Versus Host ◽

Cell Niche

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The identification of fibrosis-driving myofibroblast precursors reveals new therapeutic avenues in myelofibrosis

Blood ◽

10.1182/blood-2018-02-834820 ◽

2018 ◽

Vol 131 (19) ◽

pp. 2111-2119 ◽

Cited By ~ 22

Author(s):

Rafael Kramann ◽

Rebekka K. Schneider

Keyword(s):

Bone Marrow ◽

Stem Cell ◽

Stromal Cells ◽

Stem Cell Niche ◽

Solid Organ ◽

Hematopoietic Stem ◽

Gli Proteins ◽

Hematopoietic Stem Cell Niche ◽

Cell Niche ◽

Organ Fibrosis

Abstract Myofibroblasts are fibrosis-driving cells and are well characterized in solid organ fibrosis, but their role and cellular origin in bone marrow fibrosis remains obscure. Recent work has demonstrated that Gli1+ and LepR+ mesenchymal stromal cells (MSCs) are progenitors of fibrosis-causing myofibroblasts in the bone marrow. Genetic ablation of Gli1+ MSCs or pharmacologic targeting of hedgehog (Hh)-Gli signaling ameliorated fibrosis in mouse models of myelofibrosis (MF). Moreover, pharmacologic or genetic intervention in platelet-derived growth factor receptor α (Pdgfrα) signaling in Lepr+ stromal cells suppressed their expansion and ameliorated MF. Improved understanding of cellular and molecular mechanisms in the hematopoietic stem cell niche that govern the transition of MSCs to myofibroblasts and myofibroblast expansion in MF has led to new paradigms in the pathogenesis and treatment of MF. Here, we highlight the central role of malignant hematopoietic clone-derived megakaryocytes in reprogramming the hematopoietic stem cell niche in MF with potential detrimental consequences for hematopoietic reconstitution after allogenic stem cell transplantation, so far the only therapeutic approach in MF considered to be curative. We and others have reported that targeting Hh-Gli signaling is a therapeutic strategy in solid organ fibrosis. Data indicate that targeting Gli proteins directly inhibits Gli1+ cell proliferation and myofibroblast differentiation, which results in reduced fibrosis severity and improved organ function. Although canonical Hh inhibition (eg, smoothened [Smo] inhibition) failed to improve pulmonary fibrosis, kidney fibrosis, or MF, the direct inhibition of Gli proteins ameliorated fibrosis. Therefore, targeting Gli proteins directly might be an interesting and novel therapeutic approach in MF.

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