Quiescent Human Mesenchymal Stem Cells Are More Resistant to Heat Stress than Cycling Cells

Abstract

Quiescence is the prevailing state of many cell types under homeostatic conditions. Yet, surprisingly, little is known about how quiescent cells respond to environmental challenges. The aim of the present study is to compare stress responses of cycling and quiescent mesenchymal stem cells (MSC). Human endometrial mesenchymal cells (eMSС) were employed as adult stem cells. eMSC quiescence was modeled by serum starvation. Sublethal heat shock (HS) was used as a stress factor. Both quiescent and cycling cells were heated at 45°C for 30 min and then returned to standard culture conditions for their recovery. HS response was monitored by DNA damage response, stress-induced premature senescence (SIPS), cell proliferation activity, and oxidative metabolism. It has been found that quiescent cells repair DNA more rapidly, resume proliferation, and undergo SIPS less than proliferating cells. HS-enforced ROS production in heated cycling cells was accompanied with increased expression of genes regulating redox-active proteins. Quiescent cells exposed to HS did not intensify the ROS production, and genes involved in antioxidant defense were mostly silent. Altogether, the results have shown that quiescent cells are more resistant to heat stress than cycling cells. Next-generation sequencing (NGS) demonstrates that HS-survived cells retain differentiation capacity and do not exhibit signs of spontaneous transformation.

Three-Dimensional Compaction Switches Stress Response Programs and Enhances Therapeutic Efficacy of Endometrial Mesenchymal Stem/Stromal Cells

“…In contrast to the apoptotic reaction of 3D eMSC, heat shock induced a stop in the proliferation of damaged monolayer cells (Figure 6A), which was accompanied by a prolonged S-G 2 /M cell cycle block (Figure 6C) and expression of active senescence-associated β-galactosidase (Figure 6D). These results confirmed our previously published data and gave evidence about the induction of the SIPS program in 2D eMSC cultures that survived sublethal thermal stress (Alekseenko et al, 2014(Alekseenko et al, , 2018. To check whether 3D eMSCs that survived heat shock undergo stress-induced senescence, heated spheroids were dissociated 3 h after the stress, plated, and then were further cultured under adhesive monolayer conditions.…”

“…Our analysis of the 3D eMSC cell cycle (Domnina et al, 2018) showed that cells in spheroids do not proliferate that means they are less susceptible to the DNA-damaging stress factors. In contrast to eMSCs from spheroids, actively proliferating monolayer cells are more sensitive to the genotoxic effect of stress (Alekseenko et al, 2018).…”

Characterization of DNA Repair Foci in Root Cells of Arabidopsis in Response to DNA Damage

“…In hematopoietic stem cells of mice, non-homologous end-joining mediated repair but not HR repair is preferentially used for repair of DNA damage during the quiescence phase (Mohrin et al, 2010). The detection frequency of γH2AX foci induced by heat stress in quiescent human endometrial mesenchymal cells (MSCs) is considerably lower than that in proliferating MSCs (Alekseenko et al, 2018). Thus, it is suggested that the mechanism of DNA repair in QC cells also differs substantially from that in differentiated cells and stem cells in plants.…”

Stress-induced Cellular Senescence Contributes to Chronic Inflammation and Cancer Progression

“…Current knowledge of molecular and cellular biology of cellular senescence S. Kobashigawa et al The sensitivity of heat stress depends on the cell cycle phase. Cycling cells are found to be more sensitive to heat stress than quiescent cells 85) . In addition, cellular response to heat stress in early S phase is different than in other phases 79) .…”