Molecular Genetic Analysis of Human Endometrial Mesenchymal Stem Cells That Survived Sublethal Heat Shock

Autor: M. A. Shilina, Olga V. Anatskaya, O Tsyganov, Tatyana M. Grinchuk, Nikolay Nikolsky, A Krasnenko, A Kim, V Ilynsky, Dmitriy Korostin, Alexander E. Vinogradov, I. I. Fridlyanskaya, L. L. Alekseenko, A Elmuratov
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Zdroj: Stem Cells International, Vol 2017 (2017)
Stem Cells International
ISSN: 1687-966X
DOI: 10.1155/2017/2362630
Popis: High temperature is a critical environmental and personal factor. Although heat shock is a well-studied biological phenomenon, hyperthermia response of stem cells is poorly understood. Previously, we demonstrated that sublethal heat shock induced premature senescence in human endometrial mesenchymal stem cells (eMSC). This study aimed to investigate the fate of eMSC-survived sublethal heat shock (SHS) with special emphasis on their genetic stability and possible malignant transformation using methods of classic and molecular karyotyping, next-generation sequencing, and transcriptome functional analysis. G-banding revealed random chromosome breakages and aneuploidy in the SHS-treated eMSC. Molecular karyotyping found no genomic imbalance in these cells. Gene module and protein interaction network analysis of mRNA sequencing data showed that compared to untreated cells, SHS-survived progeny revealed some difference in gene expression. However, no hallmarks of cancer were found. Our data identified downregulation of oncogenic signaling, upregulation of tumor-suppressing and prosenescence signaling, induction of mismatch, and excision DNA repair. The common feature of heated eMSC is the silence of MYC, AKT1/PKB oncogenes, and hTERT telomerase. Overall, our data indicate that despite genetic instability, SHS-survived eMSC do not undergo transformation. After long-term cultivation, these cells like their unheated counterparts enter replicative senescence and die.
Databáze: OpenAIRE
Externí odkaz: