Distinct populations of crypt-associated fibroblasts act as signaling hubs to control colon homeostasis

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F20%3A00538133" target="_blank" >RIV/68378050:_____/20:00538133 - isvavai.cz</a>

Výsledek na webu

<a href="https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3001032" target="_blank" >https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3001032</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1371/journal.pbio.3001032" target="_blank" >10.1371/journal.pbio.3001032</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Distinct populations of crypt-associated fibroblasts act as signaling hubs to control colon homeostasis

Popis výsledku v původním jazyce

Despite recent progress in recognizing the importance of mesenchymal cells for the homeostasis of the intestinal system, the current picture of how these cells communicate with the associated epithelial layer remains unclear. To describe the relevant cell populations in an unbiased manner, we carried out a single-cell transcriptome analysis of the adult murine colon, producing a high-quality atlas of matched colonic epithelium and mesenchyme. We identify two crypt-associated colonic fibroblast populations that are demarcated by different strengths of platelet-derived growth factor receptor A (Pdgfra) expression. Crypt-bottom fibroblasts (CBFs), close to the intestinal stem cells, express low levels of Pdgfra and secrete canonical Wnt ligands, Wnt potentiators, and bone morphogenetic protein (Bmp) inhibitors. Crypt-top fibroblasts (CTFs) exhibit high Pdgfra levels and secrete noncanonical Wnts and Bmp ligands. While the Pdgfra(low) cells maintain intestinal stem cell proliferation, the Pdgfra(high) cells induce differentiation of the epithelial cells. Our findings enhance our understanding of the crosstalk between various colonic epithelial cells and their associated mesenchymal signaling hubs along the crypt axis-placing differential Pdgfra expression levels in the spotlight of intestinal fibroblast identity.

Název v anglickém jazyce

Distinct populations of crypt-associated fibroblasts act as signaling hubs to control colon homeostasis

Popis výsledku anglicky

Despite recent progress in recognizing the importance of mesenchymal cells for the homeostasis of the intestinal system, the current picture of how these cells communicate with the associated epithelial layer remains unclear. To describe the relevant cell populations in an unbiased manner, we carried out a single-cell transcriptome analysis of the adult murine colon, producing a high-quality atlas of matched colonic epithelium and mesenchyme. We identify two crypt-associated colonic fibroblast populations that are demarcated by different strengths of platelet-derived growth factor receptor A (Pdgfra) expression. Crypt-bottom fibroblasts (CBFs), close to the intestinal stem cells, express low levels of Pdgfra and secrete canonical Wnt ligands, Wnt potentiators, and bone morphogenetic protein (Bmp) inhibitors. Crypt-top fibroblasts (CTFs) exhibit high Pdgfra levels and secrete noncanonical Wnts and Bmp ligands. While the Pdgfra(low) cells maintain intestinal stem cell proliferation, the Pdgfra(high) cells induce differentiation of the epithelial cells. Our findings enhance our understanding of the crosstalk between various colonic epithelial cells and their associated mesenchymal signaling hubs along the crypt axis-placing differential Pdgfra expression levels in the spotlight of intestinal fibroblast identity.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

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OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

<a href="/cs/project/GA18-21466S" target="_blank" >GA18-21466S: Ligandy Wnt a buňky produkující tyto ligandy při obnově střevního epitelu, jeho regeneraci a v nádorech tlustého střeva mimo mutaci indukující nádor</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2020

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

P L o S Biology

ISSN

1544-9173

e-ISSN

—

Svazek periodika

18

Číslo periodika v rámci svazku

12

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

20

Strana od-do

e3001032

Kód UT WoS článku

000600098800002

EID výsledku v databázi Scopus

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