Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

HSPA1B is the Dominant Partner in the HSPA1A/HSPA1B Mediated Proteotoxic Stress Response in Placenta-Derived Stem Cells

Version 1 : Received: 5 May 2022 / Approved: 7 May 2022 / Online: 7 May 2022 (03:37:17 CEST)

How to cite: Alharbi, B.M.; Bugshan, A.; Almozel, A.; Alenzi, R.; Bouchama, A.; Khatlani, T.; Mohammad, S.; Malik, S.S. HSPA1B is the Dominant Partner in the HSPA1A/HSPA1B Mediated Proteotoxic Stress Response in Placenta-Derived Stem Cells . Preprints 2022, 2022050089 (doi: 10.20944/preprints202205.0089.v1). Alharbi, B.M.; Bugshan, A.; Almozel, A.; Alenzi, R.; Bouchama, A.; Khatlani, T.; Mohammad, S.; Malik, S.S. HSPA1B is the Dominant Partner in the HSPA1A/HSPA1B Mediated Proteotoxic Stress Response in Placenta-Derived Stem Cells . Preprints 2022, 2022050089 (doi: 10.20944/preprints202205.0089.v1).

Abstract

Placenta-derived stem cells (PDSCs) offer the advantages of possessing mesenchymal and embryonic traits, broad differentiation potential, large-scale availability, and no ethical constraints in their utilization in therapeutic applications. Elevated protein synthesis and consequently enhanced protein maintenance networks become necessary both due to the requirement to maintain stemness and respond to different stresses. This study aimed to identify the primary determinants of proteotoxic stress response in PDSCs. We generated heat-induced dose-responsive proteotoxic stress models of three stem cell types DBMSCs, DPMSCs, and pMSCs, and measured stress induction through biochemical and cell proliferation assays. RT-PCR array analysis of 84 genes involved in protein folding and protein quality control led to the identification of Hsp70 isoforms HSPA1A and HSPA1B as the prominent ones among 17 significantly expressed genes and with further analysis at the protein level through western blotting. A 24-hours’ time series analysis of stress-response allowed a detailed kinetic analysis of HSPA1A and HSPA1B gene and protein expression. More prominent differences between the two Hsp70 isoforms were detected at the translational level eluding to a potential higher requirement for HSPA1B during proteotoxic stress in PDSCs. To conclude, consideration should be given to the manipulation of definitely characterized chaperones at their expression or functional levels when utilizing PDSCs in therapeutic and regenerative applications.

Keywords

placenta-derived stem cells; placenta; stem cells; proteostasis; heat-shock; chaperones; HSPA1B; HSPA1A

Subject

MEDICINE & PHARMACOLOGY, General Medical Research

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