Department of Biomedical Sciences of Cells and Systems, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Autophagy. 2022 Feb;18(2):293-308. doi: 10.1080/15548627.2021.1924036. Epub 2021 May 19.
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 . 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.
相对静止的组织，如唾液腺（SGs），会对损伤等刺激做出反应，从而扩张、替代和再生。驻留的干细胞/祖细胞是这个过程的关键，因为它们在被激活后，具有自我更新的能力。巨自噬/自噬有助于并调节成年组织的分化，但一个重要的问题是，这条途径是否能促进组织中的干细胞自我更新。我们利用一个 3D 类器官系统来评估小鼠 SGs 干细胞（SGSCs）的自我更新能力。我们发现，休眠的 SGSCs 中的自噬通量比自我更新的 SGSCs 慢。重要的是，SGSCs 激活时自噬的增强是 3D 类器官培养和 SG 再生中自我更新的一个特征。因此，SGSCs 中的自噬缺失会抑制自我更新，而药理学刺激则会促进小鼠和人 SGSCs 的自我更新。因此，自噬是低增殖成年组织中自我更新激活的关键途径，其药理学调控有可能促进组织再生。
