Fernandes Camila Felix de Lima, Iglesia Rebeca Piatniczka, Melo-Escobar Maria Isabel, Prado Mariana Brandão, Lopes Marilene Hohmuth
Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Front Cell Dev Biol. 2019 Aug 2;7:150. doi: 10.3389/fcell.2019.00150. eCollection 2019.
Pluripotency is orchestrated by distinct players and chaperones and their partners have emerged as pivotal molecules in proteostasis control to maintain stemness. The proteostasis network consists of diverse interconnected pathways that function dynamically according to the needs of the cell to quality control and maintain protein homeostasis. The proteostasis machinery of pluripotent stem cells (PSCs) is finely adjusted in response to distinct stimuli during cell fate commitment to determine successful organism development. Growing evidence has shown different classes of chaperones regulating crucial cellular processes in PSCs. Histones chaperones promote proper nucleosome assembly and modulate the epigenetic regulation of factors involved in PSCs' rapid turnover from pluripotency to differentiation. The life cycle of pluripotency proteins from synthesis and folding, transport and degradation is finely regulated by chaperones and co-factors either to maintain the stemness status or to cell fate commitment. Here, we summarize current knowledge of the chaperone network that govern stemness and present the versatile role of chaperones in stem cells resilience. Elucidation of the intricate regulation of pluripotency, dissecting in detail molecular determinants and drivers, is fundamental to understanding the properties of stem cells in order to provide a reliable foundation for biomedical research and regenerative medicine.
多能性由不同的参与者和分子伴侣精心调控，它们的伙伴已成为蛋白质稳态控制中维持干性的关键分子。蛋白质稳态网络由多种相互连接的途径组成，这些途径根据细胞对质量控制和维持蛋白质稳态的需求动态发挥作用。多能干细胞（PSC）的蛋白质稳态机制在细胞命运决定过程中会根据不同的刺激进行精细调节，以确保生物体的成功发育。越来越多的证据表明，不同类型的分子伴侣在PSC中调节着关键的细胞过程。组蛋白分子伴侣促进正确的核小体组装，并调节参与PSC从多能性到分化快速转变的因子的表观遗传调控。多能性蛋白从合成、折叠、运输到降解的生命周期受到分子伴侣和辅助因子的精细调控，以维持干性状态或决定细胞命运。在这里，我们总结了目前关于调控干性的分子伴侣网络的知识，并展示了分子伴侣在干细胞恢复力中的多种作用。阐明多能性的复杂调控，详细剖析分子决定因素和驱动因素，对于理解干细胞的特性至关重要，以便为生物医学研究和再生医学提供可靠的基础。
