Next Article in Journal
The Association of XRCC1 Gene Polymorphisms and Chronic Hepatitis C Induced Insulin Resistance in Egyptian Patients
Previous Article in Journal
Telomere Length Calibration from qPCR Measurement: Limitations of Current Method
Article Menu

Export Article

Open AccessArticle
Cells 2018, 7(11), 184; https://doi.org/10.3390/cells7110184

Cytogenetic and Transcriptomic Analysis of Human Endometrial MSC Retaining Proliferative Activity after Sublethal Heat Shock

1
Institute of Cytology, Russian Academy of Sciences, Tikhoretskay Ave 4, St. 194064 Petersburg, Russia
2
Institute of Biomedical Chemistry (IBMC) of Russian Academy of Sciences, 10 Building 8, Pogodinskaya Street, 119121 Moscow, Russia
3
Medical Genetics Centre Genotek, Nastavnichesky Alley 17-1-15, 10510 Moscow, Russia
These authors contributed equally to this work.
These are senior authors.
*
Authors to whom correspondence should be addressed.
Received: 12 September 2018 / Revised: 19 October 2018 / Accepted: 23 October 2018 / Published: 25 October 2018
(This article belongs to the Special Issue Stem Cells in Personalized Medicine)
Full-Text   |   PDF [7727 KB, uploaded 26 October 2018]   |  

Abstract

Temperature is an important exogenous factor capable of leading to irreversible processes in the vital activity of cells. However, the long-term effects of heat shock (HS) on mesenchymal stromal cells (MSC) remain unstudied. We investigated the karyotype and DNA repair drivers and pathways in the human endometrium MSC (eMSC) survived progeny at passage 6 after sublethal heat stress (sublethal heat stress survived progeny (SHS-SP)). G-banding revealed an outbreak of random karyotype instability caused by chromosome breakages and aneuploidy. Molecular karyotyping confirmed the random nature of this instability. Transcriptome analysis found homologous recombination (HR) deficiency that most likely originated from the low thermostability of the AT-rich HR driving genes. SHS-SP protection from transformation is provided presumably by low oncogene expression maintained by tight co-regulation between thermosensitive HR drivers BRCA, ATM, ATR, and RAD51 (decreasing expression after SHS), and oncogenes mTOR, MDM2, KRAS, and EGFR. The cancer-related transcriptomic features previously identified in hTERT transformed MSC in culture were not found in SHS-SP, suggesting no traits of malignancy in them. The entrance of SHS-SP into replicative senescence after 25 passages confirms their mortality and absence of transformation features. Overall, our data indicate that SHS may trigger non-tumorigenic karyotypic instability due to HR deficiency and decrease of oncogene expression in progeny of SHS-survived MSC. These data can be helpful for the development of new therapeutic approaches in personalized medicine. View Full-Text
Keywords: human endometrial MSC; sublethal heat shock; karyotype; transcriptome; DNA repair; homologous recombination; genome instability; chromosomal breakages human endometrial MSC; sublethal heat shock; karyotype; transcriptome; DNA repair; homologous recombination; genome instability; chromosomal breakages
Figures

Graphical abstract

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material

SciFeed

Share & Cite This Article

MDPI and ACS Style

Shilina, M.A.; Grinchuk, T.M.; Anatskaya, O.V.; Vinogradov, A.E.; Alekseenko, L.L.; Elmuratov, A.U.; Nikolsky, N.N. Cytogenetic and Transcriptomic Analysis of Human Endometrial MSC Retaining Proliferative Activity after Sublethal Heat Shock. Cells 2018, 7, 184.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Cells EISSN 2073-4409 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top