Mesenchymal stem cells stimulate intestinal stem cells to repair radiation-induced intestinal injury DOI Creative Commons
Wei Gong, Mengzheng Guo,

Zhibo Han

et al.

Cell Death and Disease, Journal Year: 2016, Volume and Issue: 7(9), P. e2387 - e2387

Published: Sept. 29, 2016

Abstract The loss of stem cells residing in the base intestinal crypt has a key role radiation-induced injury. In particular, Lgr5 + (ISCs) are indispensable for regeneration following exposure to radiation. Mesenchymal (MSCs) have previously been shown improve epithelial repair mouse model radiation injury, and, therefore, it was hypothesized that this protective effect is related ISCs. study, found that, radiation, transplantation MSCs improved survival mice, ameliorated injury and increased number regenerating crypts. Furthermore, there significant increase ISCs their daughter cells, including Ki67 transient amplifying Vil1 enterocytes lysozyme Paneth response treatment with MSCs. Crypts isolated from mice treated formed higher larger enteroids than those PBS group. MSC also reduced apoptotic within small intestine at 6 h post-radiation. Interestingly, Wnt3a active β -catenin protein levels were intestines MSC-treated mice. addition, intravenous delivery recombinant after damage radioprotective, although not same degree as treatment. Our results show support growth endogenous ISCs, thus promoting molecular mechanism action mediating be activation Wnt/ signaling pathway.

Language: Английский

Tales from the crypt: new insights into intestinal stem cells DOI
Helmuth Gehart, Hans Clevers

Nature Reviews Gastroenterology & Hepatology, Journal Year: 2018, Volume and Issue: 16(1), P. 19 - 34

Published: Nov. 14, 2018

Language: Английский

Citations

794

Development of a primary human Small Intestine-on-a-Chip using biopsy-derived organoids DOI Creative Commons
Magdalena Kasendra, Alessio Tovaglieri, Alexandra Sontheimer-Phelps

et al.

Scientific Reports, Journal Year: 2018, Volume and Issue: 8(1)

Published: Feb. 7, 2018

Abstract Here we describe a method for fabricating primary human Small Intestine-on-a-Chip (Intestine Chip) containing epithelial cells isolated from healthy regions of intestinal biopsies. The are expanded as 3D organoids, dissociated, and cultured on porous membrane within microfluidic device with microvascular endothelium in parallel microchannel under flow cyclic deformation. In the Intestine Chip, epithelium forms villi-like projections lined by polarized that undergo multi-lineage differentiation similar to however, these expose their apical surfaces an open lumen interface endothelium. Transcriptomic analysis also indicates Chip more closely mimics whole duodenum vivo when compared duodenal organoids used create chips. Because fluids flowing through can be collected continuously, sequential fluid samples quantify nutrient digestion, mucus secretion establishment barrier function over period multiple days vitro . therefore may useful research tool applications where normal is crucial, including studies metabolism, nutrition, infection, drug pharmacokinetics, well personalized medicine.

Language: Английский

Citations

630

Single-cell analysis uncovers fibroblast heterogeneity and criteria for fibroblast and mural cell identification and discrimination DOI Creative Commons
Lars Muhl, Guillem Genové, Stefanos Leptidis

et al.

Nature Communications, Journal Year: 2020, Volume and Issue: 11(1)

Published: Aug. 7, 2020

Abstract Many important cell types in adult vertebrates have a mesenchymal origin, including fibroblasts and vascular mural cells. Although their biological importance is undisputed, the level of heterogeneity within between organs, while appreciated, has not been analyzed detail. Here, we compare single-cell transcriptional profiles cells across four murine muscular organs: heart, skeletal muscle, intestine bladder. We reveal gene expression signatures that demarcate from provide molecular for subtype identification. observe striking inter- intra-organ amongst fibroblasts, primarily reflecting differences extracellular matrix components. Fibroblast subtypes localize to discrete anatomical positions offering novel predictions about physiological function(s) regulatory signaling circuits. Our data shed new light on diversity poorly defined classes foundation improved understanding roles pathological processes.

Language: Английский

Citations

492

Microbiota-Derived Lactate Accelerates Intestinal Stem-Cell-Mediated Epithelial Development DOI Creative Commons
Yong Soo Lee, Tae Young Kim, Yeji Kim

et al.

Cell Host & Microbe, Journal Year: 2018, Volume and Issue: 24(6), P. 833 - 846.e6

Published: Dec. 1, 2018

Language: Английский

Citations

358

GLI1-expressing mesenchymal cells form the essential Wnt-secreting niche for colon stem cells DOI
Bahar Değirmenci, Tomáš Valenta, Slavica Dimitrieva

et al.

Nature, Journal Year: 2018, Volume and Issue: 558(7710), P. 449 - 453

Published: June 1, 2018

Language: Английский

Citations

349

Mucosal Ecological Network of Epithelium and Immune Cells for Gut Homeostasis and Tissue Healing DOI Open Access
Yosuke Kurashima, Hiroshi Kiyono

Annual Review of Immunology, Journal Year: 2017, Volume and Issue: 35(1), P. 119 - 147

Published: March 30, 2017

The intestinal epithelial barrier includes columnar epithelial, Paneth, goblet, enteroendocrine, and tuft cells as well other cell populations, all of which contribute properties essential for gastrointestinal homeostasis. mucosa is covered by mucin, contains antimicrobial peptides secretory IgA prevents luminal bacteria, fungi, viruses from stimulating immune responses. Conversely, the transport microorganisms-mediated M, dendritic, goblet cells-into tissues facilitates harmonization active quiescent mucosal bacterial population within gut-associated lymphoid creates intratissue cohabitations harmonized immunity. Intermolecular intercellular communication among immune, mesenchymal an environment conducive regeneration healing. This review summarizes so-called ecological network-the complex but vital molecular cellular interactions cells, commensal microbiota that achieve homeostasis, regeneration,

Language: Английский

Citations

255

Mucosal Profiling of Pediatric-Onset Colitis and IBD Reveals Common Pathogenics and Therapeutic Pathways DOI Creative Commons
Bing Huang, Zhanghua Chen, Lanlan Geng

et al.

Cell, Journal Year: 2019, Volume and Issue: 179(5), P. 1160 - 1176.e24

Published: Nov. 1, 2019

Language: Английский

Citations

238

The Intestinal Stem Cell Niche: Homeostasis and Adaptations DOI
António J. M. Santos,

Yuan‐Hung Lo,

Amanda T. Mah

et al.

Trends in Cell Biology, Journal Year: 2018, Volume and Issue: 28(12), P. 1062 - 1078

Published: Sept. 5, 2018

Language: Английский

Citations

222

Morphogenesis and maturation of the embryonic and postnatal intestine DOI Creative Commons
Alana M. Chin, David R. Hill, Megan Aurora

et al.

Seminars in Cell and Developmental Biology, Journal Year: 2017, Volume and Issue: 66, P. 81 - 93

Published: Feb. 2, 2017

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

Language: Английский

Citations

197

Cell plasticity in epithelial homeostasis and tumorigenesis DOI
Júlia Varga, Florian R. Greten

Nature Cell Biology, Journal Year: 2017, Volume and Issue: 19(10), P. 1133 - 1141

Published: Sept. 25, 2017

Language: Английский

Citations

188