Autophagy and pluripotency: self-eating your way to eternal youth

Macroautophagic flux is accentuated during early embryonic development and in embryonic stem cells (ESCs), and upregulation of macroautophagy facilitates reprogramming of somatic cells to iPSCs. Macroautophagy sustains quality and homeostasis of proteins and organelles in stem cells. It also remodels proteome, metabolome, and epigenome to facilitate the acquisition and maintenance of the pluripotent state. Mitophagy regulates mitochondrial integrity, dynamics, and function in stem cells. Mitophagy also reduces the number of mitochondria to enable glycolytic metabolism and minimize redox stress. Chaperone-mediated autophagy (CMA) is maintained at low levels in ESCs and is markedly increased upon differentiation. CMA modulates intracellular levels of an obligatory cofactor for DNA and histone demethylases, thereby regulating epigenetic landscape and fate decisions of ESCs. Pluripotent stem cells (PSCs) can self-renew indefinitely in culture while retaining the potential to differentiate into virtually all normal cell types in the adult animal. Due to these remarkable properties, PSCs not only provide a superb system to investigate mammalian development and model diseases, but also hold promise for regenerative therapies. Autophagy is a self-digestive process that targets proteins, organelles, and other cellular contents for lysosomal degradation. Here, we review recent literature on the mechanistic role of different types of autophagy in embryonic development, embryonic stem cells (ESCs), and induced PSCs (iPSCs), focusing on their remodeling functions on protein, metabolism, and epigenetics. We present a perspective on unsolved issues and propose that autophagy is a promising target to modulate acquisition, maintenance, and directed differentiation of PSCs. Pluripotent stem cells (PSCs) can self-renew indefinitely in culture while retaining the potential to differentiate into virtually all normal cell types in the adult animal. Due to these remarkable properties, PSCs not only provide a superb system to investigate mammalian development and model diseases, but also hold promise for regenerative therapies. Autophagy is a self-digestive process that targets proteins, organelles, and other cellular contents for lysosomal degradation. Here, we review recent literature on the mechanistic role of different types of autophagy in embryonic development, embryonic stem cells (ESCs), and induced PSCs (iPSCs), focusing on their remodeling functions on protein, metabolism, and epigenetics. We present a perspective on unsolved issues and propose that autophagy is a promising target to modulate acquisition, maintenance, and directed differentiation of PSCs. also known as tissue stem cells or somatic stem cells, are rare undifferentiated populations of cells that exist in a tissue or organ. Adult stem cells can give rise to a limited number of mature cell types that build the tissue where they reside. the process during which cells acquire specific identity, which can be affected by both extrinsic and intrinsic signals. PSCs derived from the inner cell mass of mouse or human preimplantation blastocysts and that possess the ability to self-renew and differentiate into the three primary germ layers. PSCs isolated from postimplantation epiblasts. EpiSCs were isolated from mouse embryos but not human embryos due to ethical considerations. PSCs generated directly from somatic cells by reprogramming. These cells have the capacity to self-renew and differentiate into all cell types except for cells of extraembryonic tissues. cells that can develop into the three primary germ layers of the early embryo as well as extraembryonic tissues such as the placenta.