First Author | Orhon I | Year | 2022 |
Journal | Autophagy | Volume | 18 |
Issue | 2 | Pages | 293-308 |
PubMed ID | 34009100 | Mgi Jnum | J:324328 |
Mgi Id | MGI:7257678 | Doi | 10.1080/15548627.2021.1924036 |
Citation | Orhon I, et al. (2022) Autophagy induction during stem cell activation plays a key role in salivary gland self-renewal. Autophagy 18(2):293-308 |
abstractText | Relatively quiescent tissues like salivary glands (SGs) respond to stimuli such as injury to expand, replace and regenerate. Resident stem/progenitor cells are key in this process because, upon activation, they possess the ability to self-renew. Macroautophagy/autophagy contributes to and regulates differentiation in adult tissues, but an important question is whether this pathway promotes stem cell self-renewal in tissues. We took advantage of a 3D organoid system that allows assessing the self-renewal of mouse SGs stem cells (SGSCs). We found that autophagy in dormant SGSCs has slower flux than self-renewing SGSCs. Importantly, autophagy enhancement upon SGSCs activation is a self-renewal feature in 3D organoid cultures and SGs regenerating in vivo. Accordingly, autophagy ablation in SGSCs inhibits self-renewal whereas pharmacological stimulation promotes self-renewal of mouse and human SGSCs. Thus, autophagy is a key pathway for self-renewal activation in low proliferative adult tissues, and its pharmacological manipulation has the potential to promote tissue regeneration. |