Published online Jun 26, 2021. doi: 10.4252/wjsc.v13.i6.659
Peer-review started: February 12, 2021
First decision: March 17, 2021
Revised: March 27, 2021
Accepted: May 27, 2021
Article in press: May 27, 2021
Published online: June 26, 2021
Heat shock proteins (HSPs) are molecular chaperones that protect cells against cellular stresses or injury. However, it has been increasingly recognized that they also play crucial roles in regulating fundamental cellular processes. HSP20 has been implicated in cell proliferation, but conflicting studies have shown that it can either promote or suppress proliferation. The underlying mechanisms by which HSP20 regulates cell proliferation and pluripotency remain unexplored. While the effect of HSP20 on cell proliferation has been recognized, its role in inducing pluripotency in human-induced pluripotent stem cells (iPSCs) has not been addressed.
To evaluate the efficacy of HSP20 overexpression in human iPSCs and evaluate the ability to promote cell proliferation. The purpose of this study was to investigate whether overexpression of HSP20 in iPSCs can increase pluripotency and regeneration.
We used iPSCs, which retain their potential for cell proliferation. HSP20 overexpression effectively enhanced cell proliferation and pluripotency. Overexpression of HSP20 in iPSCs was characterized by immunocytochemistry staining and real-time polymerase chain reaction. We also used cell culture, cell counting, western blotting, and flow cytometry analyses to validate HSP20 overexpression and its mechanism.
This study demonstrated that overexpression of HSP20 can increase the pluripotency in iPSCs. Furthermore, by overexpressing HSP20 in iPSCs, we showed that HSP20 upregulated proliferation markers, induced pluripotent genes, and drove cell proliferation in a sirtuin 1 (SIRT1)-dependent manner. These data have practical applications in the field of stem cell-based therapies where the mass expansion of cells is needed to generate large quantities of stem cell-derived cells for transplantation purposes.
We found that the overexpression of HSP20 enhanced the proliferation of iPSCs in a SIRT1-dependent manner. Herein, we established the distinct crosstalk between HSP20 and SIRT1 in regulating cell proliferation and pluripotency. Our study provides novel insights into the mechanisms controlling cell proliferation that can potentially be exploited to improve the expansion and pluripotency of human iPSCs for cell transplantation therapies. These results suggest that iPSCs overexpressing HSP20 exert regenerative and proliferative effects and may have the potential to improve clinical outcomes.
Core Tip: Heat shock proteins (HSPs) are housekeeper proteins that guard cells against injury and the damage response. HSPs send signals from diseased or damaged cells to the immune system, which activates the body’s defense system leading to the subsequent release of inflammatory signals that recruit other immune cells and kill the pathogen in case of infection or repair the cells in case of damage. HSPs trigger a cascade of events that involve essential proteins to accelerate the repair process or degrade injured proteins as a protection plan to ensure survival. How HSPs respond to stress or injury stimulus is a question of further investigation. Accumulating evidence indicates that HSP20 is associated with cell proliferation. However, the precise mechanisms by which HSP20 promotes stem cell proliferation remain unclear. Herein, we established the distinct crosstalk between HSP20 and sirtuin 1 in regulating cell proliferation. Our study provides a new avenue for drug discovery and treatment of critical diseases.