Autophagy in Stem Cell Biology: A Perspective on Stem Cell Self-Renewal and Differentiation

Abstract

Autophagy is a highly conserved cellular process that degrades modified, surplus, or harmful cytoplasmic components by sequestering them in autophagosomes which then fuses with the lysosome for degradation. As a major intracellular degradation and recycling pathway, autophagy is crucial for maintaining cellular homeostasis, as well as for remodeling during normal development. Impairment of this process has been implicated in various diseases, in the pathogenic response to bacterial and viral infections, and in aging. Pluripotent stem cells, with their ability to self-replicate and to give rise to any specialized cell type, are very valuable resources for cell-based medical therapies and open a number of promising avenues for studying human development and disease. It has been suggested that autophagy is vital for the maintenance of cellular homeostasis in stem cells, and subsequently more in-depth knowledge about the regulation of autophagy in stem cell biology has been acquired recently. In this review, we describe the most significant advances in the understanding of autophagy regulation in hematopoietic and mesenchymal stem cells, as well as in induced pluripotent stem cells. In particular, we highlight the roles of various autophagy activities in the regulation of self-renewal and differentiation of these stem cells.

Expression of transcriptional factor EB (TFEB) in differentiating spermatogonia potentially promotes cell migration in mouse seminiferous epithelium

“…TFEB has been characterized as a master regulator of lysosomal biogenesis and autophagy that promotes the intracellular clearance or recycling of cellular components. Notably, autophagy and endocytosis can efficiently transport sets of transcription factors, adhesion molecules, or secreted factors, and therefore has been recently recognized as a major mechanism in the regulation of self-renewal and differentiation of stem cells as well as a regulator of cell migration [ 37 – 39 ]. Meanwhile, the maintenance of sustained spermatogenesis relies on the balance between spermatogonia self-renewal and differentiation.…”

Rapamycin promotes endothelial–mesenchymal transition during stress-induced premature senescence through the activation of autophagy

“…The inhibition of mTORC1 by rapamycin is known to induce autophagy, which is involved in cell differentiation and epithelial-mesenchymal transition [43][44][45]. Next, we investigated the possible involvement of autophagy in rapamycin-induced EndMT in HCAECs subjected to SIPS.…”

The Dynamic Proteome of Oligodendrocyte Lineage Differentiation Features Planar Cell Polarity and Macroautophagy Pathways

“…To fulfill these prospects, we conducted an in-depth quantitative proteomic analysis that spanned the entire course of OL lineage cell generation in an attempt to survey the order, timing, and magnitude of proteome changes during human embryonic stem cell (hESC) differentiation into OL lineage cells. This versatile differentiation model system provides tremendous insight into human OL development, in addition to the information needed for targeted/specific cell-based medical therapies and overall disease modelling [ 4 , 5 ].…”