Unveiled the role of autophagy in salivary gland self-renewal

A work recently published in the journal Autophagy by the group led by Dr. Patricia Boya at Centro de Investigaciones Biológicas Margarita Salas shows that autophagy is essential for the self-renewal of low proliferating adult tissues, thus generating progenitor cells. Additionally, the authors demonstrate the essential role of autophagy to regenerate the damaged tissue in the event of an injury, which opens the possibility for the therapeutic potential of targeting this process.

Orhon et al. have focused on the fundamental role of autophagy in the self-renewal of the salivary glands (SGs), taking advantage of a 3D organoid system that allows to assess this process in mouse SGs stem cells (SGSCs). Results show that basal autophagy contributes to the maintenance of the SGSCs and reveal that dormant SGSCs have a slower basal autophagic flux than the progenitor cells. Accordingly, SGSCs derived from mice deficient of atg5, a gene essential for autophagy, showed a significantly lower self-renewal potential, together with less and smaller primary organoids, compared to autophagy-competent Atg5 mice. Moreover, it has been demonstrated that pharmacological stimulation of autophagy promotes self-renewal of mouse and human SGSCs.

The work has shown that 3D organoid cultures offer a unique experimental model to dissect the precise role of autophagy in this process and decipher both its precise physiological relevance in self-renewal and the regulatory connections which are established. Understanding the molecular basis of this process is key to develop efficient stem cell therapies based on autophagy modulation.

Additionally, tissue-resident stem cells cultured in the laboratory, capable of self-renewal and differentiating into adult tissues, represent an important approach aiming at future autologous cell transplantation therapies to avoid potential immune reaction. Thus, fundamental knowledge on the role of autophagy in stem cell self-renewal capacity may offer new perspectives on approaches for regenerative medicine.

This work is the result of an international collaboration between the CIB Margarita Salas and laboratories at the Departments of Biomedical Sciences of Cells and Systems and Radiation Oncology of the University Medical Center Groningen at the University of Groningen.

Reference: 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* (2021) Autophagy. DOI: 10.1080/15548627.2021.1924036