Chulabhorn International College of Medicine, Thammasat University, Rangsit Campus, Rangsit, Pathumthani, 12120, Thailand.
Laboratory of Cell-Based Assays and Innovations, School of Biotechnology, Institute of Agricultural Technology, Suranaree University of Technology, 111 University Avenue, Nakhon Ratchasima, 30000, Thailand.
Cell Tissue Res. 2018 Nov;374(2):205-216. doi: 10.1007/s00441-018-2829-7. Epub 2018 Apr 25.
Autophagy is crucial for the removal of dysfunctional organelles and protein aggregates and for maintaining stem cell homeostasis, which includes self-renewal, cell differentiation and somatic reprogramming. Loss of self-renewal capacity and pluripotency is a major obstacle to stem cell-based therapies. It has been reported that autophagy regulates stem cells under biological stimuli, starvation, hypoxia, generation of reactive oxygen species (ROS) and cellular senescence. On the one hand, autophagy is shown to play roles in self-renewal by co-function with the ubiquitin-proteasome system (UPS) to promote pluripotency-associated proteins (NANOG, OCT4 and SOX2) in human embryonic stem cells (hESCs). On the other hand, autophagy activity acts as cell reprogramming processes that play an important role for clearance fate determination and upregulates neural and cardiac differentiation. Deregulation of autophagy triggers protein disorders such as neurodegenerative cardiac/muscle diseases and cancer. Therefore, understanding of the roles of the autophagy in stem cell renewal and differentiation may benefit therapeutic development for a range of human diseases.
自噬对于去除功能失调的细胞器和蛋白质聚集体以及维持干细胞的内稳态至关重要，这包括自我更新、细胞分化和体细胞重编程。自我更新能力和多能性的丧失是基于干细胞治疗的主要障碍。据报道，自噬在生物刺激、饥饿、缺氧、活性氧（ROS）产生和细胞衰老等情况下调节干细胞。一方面，自噬通过与泛素-蛋白酶体系统（UPS）协同作用来促进人胚胎干细胞（hESC）中多能性相关蛋白（NANOG、OCT4 和 SOX2）的自我更新中发挥作用。另一方面，自噬活性作为细胞重编程过程发挥作用，对于清除命运的决定具有重要作用，并上调神经和心脏分化。自噬的失调会引发蛋白质紊乱，如神经退行性心脏/肌肉疾病和癌症。因此，了解自噬在干细胞更新和分化中的作用可能有助于开发一系列人类疾病的治疗方法。
