SCI经典句子汇总

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

摘要：

  • Autophagy is a constitutivelysosomal catabolic pathway that degrades damaged organelles and protein
  • Stem cells are characterized byself-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.
  • Novel techniques todetect autophagy in primary cells are required to study autophagy in different stem cell types.
  • These will help toelucidate the importance of autophagy in stem cells during transplantation, a promising therapeutic approach for many

前言：

  • It isnegatively regulated by serine/threonine kinase mTOR (mammalian target of rapamycin) and is a key process for cellular growth and metabolism, with its end products generating macromolecules to maintain cellular
  • The process starts withthe formation of double-membraned autophagosomes, which sequester cargo and fuse with acidic lysosomes to form autolysosomes, wherein the cargo is degraded by acid hydrolases to release the end products.
  • There are over 30 autophagy-related(Atg) genes identified so far and these genes are highly conserved among eukaryotes. Atg8 and Atg12 encode two ubiquitin-like proteins; Atg12 is conjugated to Atg5 by Atg7 and Atg10, E1 and E2-like proteins, respectively, while Atg7 and Atg3 act to conjugate Atg8/LC3-I to phosphatidylethanolamine (LC3-IPE/LC3-II).
  • On induction of autophagy, the conversion ofLC3-I into LC3-II is indicative of autophagosome formation, thus is widely used as a marker for autophagosome formation.
  • This pathway depends heavily onlysosomal activity and any defect in lysosomal degradation of autophagosomes can lead to their accumulation, impairing cell function and possibly leading to cell death by caspase activation.
  • As such, lysosomal inhibitors impair autophagic degradation;examples of these along with other pharmacological and genetic modulators are presented in Table 1.
  • Originallyviewed as a non-selective, bulk process, it is now known that specific proteins and organelles are selected and degraded by autophagy (selective autophagy) via LC3-interacting adaptors such as p62 and NBR1 and autophagy receptors like Nix.
  • Moreover, asan intracellular recycling pathway autophagy plays a crucial role in the active elimination of unnecessary proteins and organelles, such as those that accumulate during the dynamic programme of stem cell renewal, proliferation and differentiation.
  • It not onlyprovides bioenergetics support for these events but also takes care of apoptotic bodies generated during the process.
  • Stem cells arenon-specialized cells capable of differentiating into many different types of mature cells while maintaining the stem cell population through self-replication.
  • Stem cellsare long-lived and undergo lengthy periods of quiescence.
  • We hypothesize thatthese unique properties of stem cells, namely (1) pluripotency and differentiation, (2) self-renewal, and (3) quiescence require autophagy.
  • Autophagy,as a highly inducible catabolic process, plays a pivotal role in the attainment of precise morphology and function by controlling protein turnover via mTOR regulation.
  • A fast and efficient removal of sets of transcriptionfactors, enzymes, adhesion molecules, or released factors can be efficiently accomplished by autophagy, this being a great advantage for both differentiation and renewal.
  • Forexample, mitophagy is essential to preserve the ‘stemness’ or pluripotency of embryonic stem cells within in vitro long-term cultures by resisting genetic and/or mitochondrial damage.
  • Depending ontheir location in the body and the type of cells they produce, stem cells can be classified as embryonic stem cells (ESCs) and adult stem cells (ASCs).
  • Finallywe will address how it can be modulated for stem cell-based gene therapy and other stem cell targeting approaches.
  • Stem cells are a very rare populationwithin tissues, making them difficult to identify and therefore difficult to
  • Beingsmall populations with a combination of multiple markers required to define them, stem cells call for more modern techniques in order to study their autophagy levels.

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