Chaperones and Beyond as Key Players in Pluripotency Maintenance

Abstract

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.

Epigenetic Regulation of Dental Pulp Stem Cell Fate

“…While most studies were mainly conducted in vitro , further investigations, including in vivo experiments and animal disease models, would be needed to explore the clinical potential in disease treatment and regenerative medicine such as HDACis and DNMT inhibitors related to epigenetic modifications. In addition, some other epigenetic modifications such as RNA modification and chaperones have been shown to be involved in embryo development, cell differentiation, and pluripotency maintenance [ 185 – 188 ]. It would be necessary to reach deeper insights into the role of these epigenetic modifications in the modulation of DPSC fate.…”

Heat Shock Proteins in Glioblastoma Biology: Where Do We Stand?

“…HOP mediates the protein complex formed by HSP70 and HSP90 and acts as a molecular “bridge” that allows physical binding of these two chaperones (reviewed in [1]). The proteostasis machinery formed by this complex is highly important for proteome quality control in numerous different cell types, such as pluripotent stem cells (briefly reviewed in [2]), but also in cancer and, in particular, in GBM cells.…”

“…In addition to HSPs, there are other classes of chaperones that present relevant roles in GSC biology, demonstrating the importance of these molecules for GBM maintenance. For example, histone chaperones, which can modulate epigenetic modifications that lead to a differential pattern of transcription factors expression [2].…”

“…Chaperone proteins play a fundamental role in assisting protein synthesis, folding, remodeling, targeting, and inhibition of non-functional and potentially pathogenic protein aggregate formation, being essential players for the maintenance of proteome homeostasis (i.e., proteostasis) [1]. An important and vast group of chaperones is induced by heat shock and is denominated heat shock proteins (HSPs) [2]. Besides their role in proteostasis, HSPs can also act in antigen presentation, hormone receptor assembly, secretion, and cellular trafficking [3].…”

Protein quality control of cell stemness

“…Other aspects of regulation, such as miRNAs and epigenetic modifications, have also been studied extensively (Atlasi and Stunnenberg, 2017 ; Avgustinova and Benitah, 2016 ; Croce and Calin, 2005 ; Foshay and Gallicano, 2009 ; Hsieh and Gage, 2004 ; Martinez and Gregory, 2010 ; Meissner, 2010 ; Shenoy and Blelloch, 2014 ; Wang et al, 2007 ; Wu and Sun, 2006 ; Yu et al, 2012 ). Although there has been less focus on posttranslational mechanisms of regulation, recent studies indicate that there is a close connection between protein quality control (PQC) and stem cell function (Assou et al, 2009 ; Bradley et al, 2012 ; Buckley et al, 2012 ; Fernandes et al, 2019 ; García-Prat et al, 2017 ; Geng et al, 2015 ; Heijmans et al, 2013 ; Hernebring et al, 2013 ; Jang et al, 2014 ; Kapetanou et al, 2017 ; Noormohammadi et al, 2018 ; Saretzki et al, 2004 ; Schroter and Adjaye, 2014 ; Vilchez et al, 2013 ).…”