Open AccessExtracellular vesicles transmit epithelial growth factor activity in the intestinal stem cell niche
Author(s) -
Oszvald Ádám,
Szvicsek Zsuzsanna,
Sándor Gyöngyvér Orsolya,
Kelemen Andrea,
Soós András Áron,
Pálóczi Krisztina,
Bursics Attila,
Dede Kristóf,
Tölgyes Tamás,
Buzás Edit I.,
Zeöld Anikó,
Wiener Zoltán
Publication year - 2020
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.3113
Subject(s) - biology , microbiology and biotechnology , amphiregulin , epidermal growth factor , stem cell , wnt signaling pathway , organoid , fibroblast growth factor , lgr5 , intestinal epithelium , fibroblast , immunology , epithelium , cell culture , signal transduction , biochemistry , genetics , receptor
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.