Tightrope act: autophagy in stem cell renewal, differentiation, proliferation, and aging

Abstract

Autophagy is a constitutive lysosomal catabolic pathway that degrades damaged organelles and protein aggregates. Stem cells are characterized by self-renewal, pluripotency, and quiescence; their long life span, limited capacity to dilute cellular waste and spent organelles due to quiescence, along with their requirement for remodeling in order to differentiate, all suggest that they require autophagy more than other cell types. Here, we review the current literature on the role of autophagy in embryonic and adult stem cells, including hematopoietic, mesenchymal, and neuronal stem cells, highlighting the diverse and contrasting roles autophagy plays in their biology. Furthermore, we review the few studies on stem cells, lysosomal activity, and autophagy. Novel techniques to detect autophagy in primary cells are required to study autophagy in different stem cell types. These will help to elucidate the importance of autophagy in stem cells during transplantation, a promising therapeutic approach for many diseases.

Mesenchymal Stromal Cells Deficient in Autophagy Proteins Are Susceptible to Oxidative Injury and Mitochondrial Dysfunction

“…Our study showed that autophagic proteins play a critical role in regulating MSC survival under oxidative stress. Survival of MSCs after transplantation in damaged myocardium can be enhanced by autophagy-activating drugs (47). The process of autophagy could contribute to the engraftment of transplanted MSCs used in therapy, and lends itself to an application of prolonging survival of MSCs (47,48).…”

Role of autophagy in the maintenance and function of cancer stem cells

“…This catabolic process is indeed involved in the preservation of stem cell homeostasis and the maintenance of stemness property (reviewed in (Guan et al, 2013, Phadwal et al, 2013, Vessoni et al, 2012). Of note, the protein/organelle quality control operated by autophagy appears of particular relevance during periods of quiescence and/ or differentiation (Guan et al, 2013).…”

Autophagy in stem cells

“…Indeed, consideration of the available data suggests that the unique properties of stem cells (self-renewal, pluripotency, differentiation and quiescence) are dependent on the activation of the autophagic process. 12,13 First, the processes of self-renewal and differentiation both require a strict control of cellular remodeling that involves protein turnover and lysosomal degradation of organelles.…”