Autophagy induction during stem cell activation plays a key role in salivary gland self-renewal. Issue 2 (1st February 2022)

• Record Type: Journal Article
• Authors: Orhon, Idil; Rocchi, Cecilia; Villarejo-Zori, Beatriz; Serrano Martinez, Paola; Baanstra, Mirjam; Brouwer, Uilke; Boya, Patricia; Coppes, Rob; Reggiori, Fulvio
• Is Part Of: Autophagy. Volume 18:Issue 2(2022)
• Page Start: 293
• Page End: 308
• Publication Date: 2022-02-01
• Subjects: Autophagy -- maintenance -- salivary glands -- self-renewal -- stem cells; Autophagic vacuoles -- Periodicals; Apoptosis -- Periodicals; Cell death -- Periodicals; Lysosomes -- Periodicals; Degeneration (Pathology) -- Periodicals; Autophagy -- Periodicals; Cell Death -- Periodicals; Lysosomes -- Periodicals; Periodicals; 571.936
• DOI: 10.1080/15548627.2021.1924036
• Languages: English
• ISSNs: 1554-8627

Abstract

ABSTRACT: 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.