Autophagy induction during stem cell activation plays a key role in salivary gland self-renewal

Idil Orhon, Cecilia Rocchi, Beatriz Villarejo-Zori, Paola Serrano Martinez, Mirjam Baanstra, Uilke Brouwer, Patricia Boya, Rob Coppes, Fulvio Reggiori

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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.

Original languageEnglish
Pages (from-to)1-16
Number of pages16
JournalAutophagy
DOIs
Publication statusPublished - 19-May-2021

Keywords

  • Autophagy
  • maintenance
  • salivary glands
  • self-renewal
  • stem cells
  • REGENERATION
  • METABOLISM
  • MAINTAINS
  • SWITCH

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