Short heat shock has a long-term effect on mesenchymal stem cells’ transcriptome

Ivana Ribarski-Chorev; Gisele Schudy; Carmit Strauss; Sharon Schlesinger

doi:10.1016/j.isci.2023.107305

Short heat shock has a long-term effect on mesenchymal stem cells’ transcriptome

Ivana Ribarski-Chorev, Gisele Schudy, Carmit Strauss, Sharon Schlesinger^*

^*Corresponding author for this work

Department of Animal Sciences

Research output: Contribution to journal › Article › peer-review

Abstract

The adverse effects of heat stress (HS) on physiological systems are well documented, yet the underlying molecular mechanisms behind it remain poorly understood. To address this knowledge gap, we conducted a comprehensive investigation into the impact of HS on mesenchymal stem cells (MSCs), focusing on their morphology, phenotype, proliferative capacity, and fate determination. Our in-depth analysis of the MSCs’ transcriptome revealed a significant influence of HS on the transcriptional landscape. Notably, even after a short period of stress, we observed a persistent alteration in cell identity, potentially mediated by the activation of bivalent genes. Furthermore, by comparing the differentially expressed genes following short HS with their transcriptional state after recovery, we identified the transient upregulation of MLL and other histone modifiers, providing a potential mechanistic explanation for the stable activation of bivalent genes. This could be used to predict and modify the long-term effect of HS on cell identity.

Original language	American English
Article number	107305
Journal	iScience
Volume	26
Issue number	8
DOIs	https://doi.org/10.1016/j.isci.2023.107305
State	Published - 18 Aug 2023

Bibliographical note

Funding Information:
This work was funded by a US-Israel Binational Agricultural Research and Development Fund research project #IS-5067-18, The Israeli Dairy Board grant # 820-0341 and the Israeli Ministry of Agriculture and Rural Development grant #12- 04-0014. We are grateful to all the members of the Schlesinger lab for their ideas and support; Dr. Asaf Marco for help with the bioinformatic analysis, Prof. Z. Roth for scientific discussion, encouragement and support; Joseph Kippen for critical reading and reviewing; the Weizmann Institute Next Generation Sequencing Facility, for sequencing support; The authors also thank Dr. S. Shainin and Mr. S. Yaakobi from the Volcani Center for help with obtaining the umbilical cords. Graphical abstract was Created with BioRender.com. I.R.H.: conception and design, designing and performed the experiments, bioinformatics analysis and data interpretation, and manuscript writing. G.S.: validation of MSC lines by flow and RT-qPCR. C.S.: support with MSC extraction and culturing. S.S.: conception and design, assembly of data and data analysis, manuscript writing. The authors read and approved the final manuscript. The authors declare that they have no competing interests. We support inclusive, diverse, and equitable conduct of research.

Funding Information:
This work was funded by a US-Israel Binational Agricultural Research and Development Fund research project #IS-5067-18 , The Israeli Dairy Board grant # 820-0341 and the Israeli Ministry of Agriculture and Rural Development grant #12- 04-0014 . We are grateful to all the members of the Schlesinger lab for their ideas and support; Dr. Asaf Marco for help with the bioinformatic analysis, Prof. Z. Roth for scientific discussion, encouragement and support; Joseph Kippen for critical reading and reviewing; the Weizmann Institute Next Generation Sequencing Facility, for sequencing support; The authors also thank Dr. S. Shainin and Mr. S. Yaakobi from the Volcani Center for help with obtaining the umbilical cords. Graphical abstract was Created with BioRender.com .

Publisher Copyright:
© 2023 The Author(s)

Keywords

Biological sciences
Cell biology
Stem cells research

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10.1016/j.isci.2023.107305

Cite this

@article{ae7919b44c054825a1709745bfab8935,

title = "Short heat shock has a long-term effect on mesenchymal stem cells{\textquoteright} transcriptome",

abstract = "The adverse effects of heat stress (HS) on physiological systems are well documented, yet the underlying molecular mechanisms behind it remain poorly understood. To address this knowledge gap, we conducted a comprehensive investigation into the impact of HS on mesenchymal stem cells (MSCs), focusing on their morphology, phenotype, proliferative capacity, and fate determination. Our in-depth analysis of the MSCs{\textquoteright} transcriptome revealed a significant influence of HS on the transcriptional landscape. Notably, even after a short period of stress, we observed a persistent alteration in cell identity, potentially mediated by the activation of bivalent genes. Furthermore, by comparing the differentially expressed genes following short HS with their transcriptional state after recovery, we identified the transient upregulation of MLL and other histone modifiers, providing a potential mechanistic explanation for the stable activation of bivalent genes. This could be used to predict and modify the long-term effect of HS on cell identity.",

keywords = "Biological sciences, Cell biology, Stem cells research",

author = "Ivana Ribarski-Chorev and Gisele Schudy and Carmit Strauss and Sharon Schlesinger",

note = "Funding Information: This work was funded by a US-Israel Binational Agricultural Research and Development Fund research project #IS-5067-18, The Israeli Dairy Board grant # 820-0341 and the Israeli Ministry of Agriculture and Rural Development grant #12- 04-0014. We are grateful to all the members of the Schlesinger lab for their ideas and support; Dr. Asaf Marco for help with the bioinformatic analysis, Prof. Z. Roth for scientific discussion, encouragement and support; Joseph Kippen for critical reading and reviewing; the Weizmann Institute Next Generation Sequencing Facility, for sequencing support; The authors also thank Dr. S. Shainin and Mr. S. Yaakobi from the Volcani Center for help with obtaining the umbilical cords. Graphical abstract was Created with BioRender.com. I.R.H.: conception and design, designing and performed the experiments, bioinformatics analysis and data interpretation, and manuscript writing. G.S.: validation of MSC lines by flow and RT-qPCR. C.S.: support with MSC extraction and culturing. S.S.: conception and design, assembly of data and data analysis, manuscript writing. The authors read and approved the final manuscript. The authors declare that they have no competing interests. We support inclusive, diverse, and equitable conduct of research. Funding Information: This work was funded by a US-Israel Binational Agricultural Research and Development Fund research project #IS-5067-18 , The Israeli Dairy Board grant # 820-0341 and the Israeli Ministry of Agriculture and Rural Development grant #12- 04-0014 . We are grateful to all the members of the Schlesinger lab for their ideas and support; Dr. Asaf Marco for help with the bioinformatic analysis, Prof. Z. Roth for scientific discussion, encouragement and support; Joseph Kippen for critical reading and reviewing; the Weizmann Institute Next Generation Sequencing Facility, for sequencing support; The authors also thank Dr. S. Shainin and Mr. S. Yaakobi from the Volcani Center for help with obtaining the umbilical cords. Graphical abstract was Created with BioRender.com . Publisher Copyright: {\textcopyright} 2023 The Author(s)",

year = "2023",

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doi = "10.1016/j.isci.2023.107305",

language = "American English",

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AU - Schudy, Gisele

AU - Strauss, Carmit

AU - Schlesinger, Sharon

N1 - Funding Information: This work was funded by a US-Israel Binational Agricultural Research and Development Fund research project #IS-5067-18, The Israeli Dairy Board grant # 820-0341 and the Israeli Ministry of Agriculture and Rural Development grant #12- 04-0014. We are grateful to all the members of the Schlesinger lab for their ideas and support; Dr. Asaf Marco for help with the bioinformatic analysis, Prof. Z. Roth for scientific discussion, encouragement and support; Joseph Kippen for critical reading and reviewing; the Weizmann Institute Next Generation Sequencing Facility, for sequencing support; The authors also thank Dr. S. Shainin and Mr. S. Yaakobi from the Volcani Center for help with obtaining the umbilical cords. Graphical abstract was Created with BioRender.com. I.R.H.: conception and design, designing and performed the experiments, bioinformatics analysis and data interpretation, and manuscript writing. G.S.: validation of MSC lines by flow and RT-qPCR. C.S.: support with MSC extraction and culturing. S.S.: conception and design, assembly of data and data analysis, manuscript writing. The authors read and approved the final manuscript. The authors declare that they have no competing interests. We support inclusive, diverse, and equitable conduct of research. Funding Information: This work was funded by a US-Israel Binational Agricultural Research and Development Fund research project #IS-5067-18 , The Israeli Dairy Board grant # 820-0341 and the Israeli Ministry of Agriculture and Rural Development grant #12- 04-0014 . We are grateful to all the members of the Schlesinger lab for their ideas and support; Dr. Asaf Marco for help with the bioinformatic analysis, Prof. Z. Roth for scientific discussion, encouragement and support; Joseph Kippen for critical reading and reviewing; the Weizmann Institute Next Generation Sequencing Facility, for sequencing support; The authors also thank Dr. S. Shainin and Mr. S. Yaakobi from the Volcani Center for help with obtaining the umbilical cords. Graphical abstract was Created with BioRender.com . Publisher Copyright: © 2023 The Author(s)

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N2 - The adverse effects of heat stress (HS) on physiological systems are well documented, yet the underlying molecular mechanisms behind it remain poorly understood. To address this knowledge gap, we conducted a comprehensive investigation into the impact of HS on mesenchymal stem cells (MSCs), focusing on their morphology, phenotype, proliferative capacity, and fate determination. Our in-depth analysis of the MSCs’ transcriptome revealed a significant influence of HS on the transcriptional landscape. Notably, even after a short period of stress, we observed a persistent alteration in cell identity, potentially mediated by the activation of bivalent genes. Furthermore, by comparing the differentially expressed genes following short HS with their transcriptional state after recovery, we identified the transient upregulation of MLL and other histone modifiers, providing a potential mechanistic explanation for the stable activation of bivalent genes. This could be used to predict and modify the long-term effect of HS on cell identity.

AB - The adverse effects of heat stress (HS) on physiological systems are well documented, yet the underlying molecular mechanisms behind it remain poorly understood. To address this knowledge gap, we conducted a comprehensive investigation into the impact of HS on mesenchymal stem cells (MSCs), focusing on their morphology, phenotype, proliferative capacity, and fate determination. Our in-depth analysis of the MSCs’ transcriptome revealed a significant influence of HS on the transcriptional landscape. Notably, even after a short period of stress, we observed a persistent alteration in cell identity, potentially mediated by the activation of bivalent genes. Furthermore, by comparing the differentially expressed genes following short HS with their transcriptional state after recovery, we identified the transient upregulation of MLL and other histone modifiers, providing a potential mechanistic explanation for the stable activation of bivalent genes. This could be used to predict and modify the long-term effect of HS on cell identity.

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DO - 10.1016/j.isci.2023.107305

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AN - SCOPUS:85165332687

SN - 2589-0042

VL - 26

JO - iScience

JF - iScience

IS - 8

M1 - 107305

ER -

Short heat shock has a long-term effect on mesenchymal stem cells’ transcriptome

Abstract

Bibliographical note

Keywords

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