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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Journal ArticleDOI
Cellular Plasticity in Intestinal Homeostasis and Disease
TL;DR: The mechanistic principles and key players involved in intestinal plasticity are reviewed and potential therapeutic implications of cellular plasticity in regenerative medicine and cancer are discussed.
Journal ArticleDOI
Lgr5+ telocytes are a signaling source at the intestinal villus tip
Keren Bahar Halpern,Hassan Massalha,Rachel K. Zwick,Andreas E. Moor,David Castillo-Azofeifa,Milena Rozenberg,Lydia Farack,Adi Egozi,Dan R. Miller,Inna Averbukh,Yotam Harnik,Noa Weinberg-Corem,Frederic J. de Sauvage,Ido Amit,Ophir D. Klein,Michal Shoshkes-Carmel,Shalev Itzkovitz +16 more
TL;DR: A spatially-resolved cell atlas of the small intestinal stroma is provided and Lgr5 + villus tip telocytes are exposed as regulators of the epithelial spatial expression programs along the villus axis, revealing spatially zonation of mesenchymal cells along the crypt-villus axis.
Journal ArticleDOI
Lats1/2 Sustain Intestinal Stem Cells and Wnt Activation through TEAD-Dependent and Independent Transcription
Qi Li,Yang Sun,Gopala K. Jarugumilli,Shun Liu,Kyvan Dang,Jennifer L. Cotton,Jordi Xiol,Jordi Xiol,PuiYee Chan,Michael DeRan,Lifang Ma,Rui Li,Lihua Julie Zhu,Joyce Li,Andrew B. Leiter,Y. Tony Ip,Fernando D. Camargo,Fernando D. Camargo,Xuelian Luo,Randy L. Johnson,Xu Wu,Junhao Mao +21 more
TL;DR: It is demonstrated that Lats1/2, the core Hippo kinases, are essential to maintain Wnt pathway activity and intestinal stem cells and that intestinal Wnt inhibition by Lats deletion is Yes-associated protein (YAP)/transcriptional activator with PDZ-binding domain (TAZ) dependent but TEAD independent.
Journal ArticleDOI
Tales from the crypt: intestinal niche signals in tissue renewal, plasticity and cancer
TL;DR: Recent developments in the understanding of intestinal stem cell dynamics are reviewed, focusing on the roles, mechanisms and interconnectivity of prime signalling pathways that regulate stem cell behaviour in intestinal homeostasis.
Journal ArticleDOI
Mapping Development of the Human Intestinal Niche at Single-Cell Resolution.
Emily M. Holloway,Michael Czerwinski,Yu-Hwai Tsai,Joshua H. Wu,Angeline Wu,Charlie Childs,Katherine D. Walton,Caden W. Sweet,Qianhui Yu,Ian A. Glass,Barbara Treutlein,J. Gray Camp,Jason R. Spence +12 more
TL;DR: This work uses single-cell mRNA sequencing with in situ validation approaches to interrogate human intestinal development from 7-21 weeks post conception, assigning molecular identities and spatial locations to cells and factors that comprise the niche.
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Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts
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