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Extracellular vesicles transmit epithelial growth factor activity in the intestinal stem cell niche.
STEM CELLS ( IF 5.614 ) Pub Date : 2019-11-23 , DOI: 10.1002/stem.3113
Ádám Oszvald,Zsuzsanna Szvicsek,Gyöngyvér Orsolya Sándor,Andrea Kelemen,András Áron Soós,Krisztina Pálóczi,Attila Bursics,Kristóf Dede,Tamás Tölgyes,Edit I Buzás,Anikó Zeöld,Zoltán Wiener

Extracellular vesicles (EV) are membrane-surrounded vesicles that represent a novel way of intercellular communication by carrying biologically important molecules in a concentrated and protected form. The intestinal epithelium is continuously renewed by a small proliferating intestinal stem cell (ISC) population, residing at the bottom of the intestinal crypts in a specific microenvironment, the stem cell niche. By using 3D mouse and human intestinal organoids, we show that intestinal fibroblast-derived EVs are involved in forming the ISC niche by transmitting Wnt and epidermal growth factor (EGF) activity. With a mouse model that expresses EGFP in the Lgr5+ ISCs, we prove that loss in ISC number in the absence of EGF is prevented by fibroblast-derived EVs. Furthermore, we demonstrate that intestinal fibroblast-derived EVs carry EGF family members, such as amphiregulin. Mechanistically, blocking EV-bound amphiregulin inhibited the EV-induced survival of organoids. In contrast, EVs have no role in transporting R-Spondin, a critical niche factor amplifying Wnt signaling. Collectively, we prove the important role of fibroblast-derived EVs as a novel transmission mechanism of factors in the normal ISC niche.
更新日期:2019-11-26

 

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