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
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Novel variants in the stem cell niche factor WNT2B define the disease phenotype as a congenital enteropathy with ocular dysgenesis.
Yanjia Jason Zhang,Lissette Jimenez,Svetlana Azova,Jessica Kremen,Yee-Ming Chan,Abdelrahman M. Elhusseiny,Hajirah N. Saeed,Jeff Goldsmith,Alyaa Al-Ibraheemi,Amy E. O’Connell,Olga Kovbasnjuk,Lance H. Rodan,Pankaj B. Agrawal,Jay R. Thiagarajah +13 more
TL;DR: This growing case series suggests that variants in WNT2B are associated with an oculo-intestinal (and possibly gonadal) syndrome, due to the protein’s putative involvement in multiple developmental and stem cell maintenance pathways.
Journal ArticleDOI
Roles of pulmonary telocytes in airway epithelia to benefit experimental acute lung injury through production of telocyte-driven mediators and exosomes
TL;DR: In this paper , the authors explored the direct roles of Telocytes and the roles of TC-derived exosomes in support of experimental acute lung injury (ALI) in vivo or in vitro, and showed that TCs mainly prevented from lung tissue edema and hemorrhage and decreased the levels of VEGF-A and MMP9 induced by LPS.
Journal ArticleDOI
Robust Colonic Epithelial Regeneration and Amelioration of Colitis via FZD-Specific Activation of Wnt Signaling
Lei Xie,Russell Fletcher,Diksha Bhatia,Darshini Shah,J. M. Phipps,S Deshmukh,Haili Zhang,Jingjing Ye,Sungjin Lee,Lucas Le,Maureen Newman,Hui-Juan Chen,Asmiti Sura,Suhani Gupta,Laura E. Sanman,Fan Yang,Weixu Meng,Helene Baribault,Geertrui F. Vanhove,Wen-Chen Yeh,Yang Li,Chen Lu +21 more
TL;DR: In this paper , the effects of Wnt mimetics with subfamily Fzd specificities were examined in an acute dextran sulfate (DSS) mouse colitis model, and it was shown that SZN-1326-p directly impacted epithelial cells, driving transient expansion of stem and progenitor cells, promoting differentiation of epithel cells, histologically restoring the damaged epithelium, and secondarily to epithelial repair.
Journal Article
Telocytes enhanced in vitro decidualization and mesenchymal-epithelial transition in endometrial stromal cells via Wnt/β-catenin signaling pathway.
TL;DR: This is the first study to show that TCs can enhance decidualization and MET in ESCs through the Wnt/β-catenin signaling-pathway, and describes a promising cell therapy for gynecological conditions and related reproductive problems associated with defective decidUALization.
Journal ArticleDOI
Injury-Induced Cellular Plasticity Drives Intestinal Regeneration
TL;DR: The ability for intestinal epithelial cells to revert to a stem cell state is an important physiological damage response to regenerate the intestinal epithelium at sites of mucosal injury as discussed by the authors .
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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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