Subepithelial telocytes are an important source of Wnts that supports intestinal crypts
Michal Shoshkes-Carmel,Yue J. Wang,Kirk J. Wangensteen,Beáta Tóth,Ayano Kondo,Efi E. Massasa,Shalev Itzkovitz,Klaus H. Kaestner +7 more
TLDR
Subepithelial telocytes are identified as a source of Wnt signals that enable proliferation and differentiation of intestinal stem cells, an essential function for maintenance of the intestinal epithelium.Abstract:
Tissues that undergo rapid cellular turnover, such as the mammalian haematopoietic system or the intestinal epithelium, are dependent on stem and progenitor cells that proliferate to provide differentiated cells to maintain organismal health. Stem and progenitor cells, in turn, are thought to rely on signals and growth factors provided by local niche cells to support their function and self-renewal. Several cell types have been hypothesized to provide the signals required for the proliferation and differentiation of the intestinal stem cells in intestinal crypts1-6. Here we identify subepithelial telocytes as an important source of Wnt proteins, without which intestinal stem cells cannot proliferate and support epithelial renewal. Telocytes are large but rare mesenchymal cells that are marked by expression of FOXL1 and form a subepithelial plexus that extends from the stomach to the colon. While supporting the entire epithelium, FOXL1+ telocytes compartmentalize the production of Wnt ligands and inhibitors to enable localized pathway activation. Conditional genetic ablation of porcupine (Porcn), which is required for functional maturation of all Wnt proteins, in mouse FOXL1+ telocytes causes rapid cessation of Wnt signalling to intestinal crypts, followed by loss of proliferation of stem and transit amplifying cells and impaired epithelial renewal. Thus, FOXL1+ telocytes are an important source of niche signals to intestinal stem cells.read more
Citations
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Essential role of IFN-γ in T cell–associated intestinal inflammation
Yoshihiro Eriguchi,Kiminori Nakamura,Yuki Yokoi,Rina Sugimoto,Shuichiro Takahashi,Daigo Hashimoto,Takanori Teshima,Tokiyoshi Ayabe,Michael E. Selsted,Andre J. Ouellette +9 more
TL;DR: IFN-γ induced Paneth cell death and impaired regeneration of small intestinal epithelium in vivo, suggesting that IFN-α may be a useful target for treating defective mucosal regeneration in enteric inflammation.
Journal ArticleDOI
High-fat diet-activated fatty acid oxidation mediates intestinal stemness and tumorigenicity
Miyeko D. Mana,Miyeko D. Mana,Amanda M. Hussey,Constantine N. Tzouanas,Shinya Imada,Yesenia Barrera Millan,Dorukhan Bahceci,Dominic R. Saiz,Anna T. Webb,Caroline A. Lewis,Peter Carmeliet,Peter Carmeliet,Peter Carmeliet,Maria M. Mihaylova,Alex K. Shalek,Ömer H. Yilmaz,Ömer H. Yilmaz,Ömer H. Yilmaz +17 more
TL;DR: In this article, the authors found that PPARα and PPARδ contribute to the HFD response in ISCs by robustly inducing a downstream fatty acid oxidation (FAO) metabolic program.
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Single cell and genetic analyses reveal conserved populations and signaling mechanisms of gastrointestinal stromal niches.
Ji-Eun Kim,Lijiang Fei,Wen-Chi Yin,Sabrina Coquenlorge,Abilasha Rao-Bhatia,Xiaoyun Zhang,Sammy Shun Wai Shi,Ju Hee Lee,Noah A. Hahn,Wasi Rizvi,Kyoung-Han Kim,Hoon Ki Sung,Chi-chung Hui,Guoji Guo,Tae-Hee Kim +14 more
TL;DR: A conserved population of stromal cells adjacent to stomach epithelia where Gli2 activates Wnt ligands to promote gastrointestinal regeneration and development is identified by performing single cell analysis.
Journal ArticleDOI
Wnt Signaling in 3D: Recent Advances in the Applications of Intestinal Organoids.
TL;DR: How alterations in growth factor dependency and organoid morphology can be exploited to identify Wnt signaling mechanisms, characterize mutated pathway components, and predict responses of patient-derived tumors to targeted therapy is reviewed.
Journal ArticleDOI
Emerging role of contact-mediated cell communication in tissue development and diseases
Benjamin Mattes,Steffen Scholpp +1 more
TL;DR: These signalling protrusions emerge as essential structural components of a vibrant communication network in the development and tissue homeostasis of any multicellular organism and are starting to understand the morphology and function in many tissues.
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Journal ArticleDOI
Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts
Toshiro Sato,Johan H. van Es,Hugo J. Snippert,Daniel E. Stange,Robert G.J. Vries,Maaike van den Born,Nick Barker,Noah F. Shroyer,Marc van de Wetering,Hans Clevers +9 more
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