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Embryonic stem cells become mechanoresponsive upon exit from ground state of pluripotency

Stem cell fate decisions are driven by a broad array of signals, both chemical and mechanical. Although much progress has been made in our understanding of the impact of chemical signals on cell fate choice, much less is known about the role and influence of mechanical signalling, particularly in em...

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Detalles Bibliográficos
Autores principales: Verstreken, C. M., Labouesse, C., Agley, C. C., Chalut, K. J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6367133/
https://www.ncbi.nlm.nih.gov/pubmed/30958114
http://dx.doi.org/10.1098/rsob.180203
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author Verstreken, C. M.
Labouesse, C.
Agley, C. C.
Chalut, K. J.
author_facet Verstreken, C. M.
Labouesse, C.
Agley, C. C.
Chalut, K. J.
author_sort Verstreken, C. M.
collection PubMed
description Stem cell fate decisions are driven by a broad array of signals, both chemical and mechanical. Although much progress has been made in our understanding of the impact of chemical signals on cell fate choice, much less is known about the role and influence of mechanical signalling, particularly in embryonic stem (ES) cells. Many studies use substrates with different stiffness to study mechanical signalling, but changing substrate stiffness can induce secondary effects which are difficult to disentangle from the direct effects of forces/mechanical signals. To probe the direct impact of mechanical stress on cells, we developed an adaptable cell substrate stretcher to exert specific, reproducible forces on cells. Using this device to test the response of ES cells to tensile strain, we found that cells experienced a transient influx of calcium followed by an upregulation of the so-called immediate and early genes. On longer time scales, however, ES cells in ground state conditions were largely insensitive to mechanical stress. Nonetheless, as ES cells exited the ground state, their susceptibility to mechanical signals increased, resulting in broad transcriptional changes. Our findings suggest that exit from ground state of pluripotency is unaffected by mechanical signals, but that these signals could become important during the next stage of lineage specification. A better understanding of this process could improve our understanding of cell fate choice in early development and improve protocols for differentiation guided by mechanical cues.
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spelling pubmed-63671332019-02-22 Embryonic stem cells become mechanoresponsive upon exit from ground state of pluripotency Verstreken, C. M. Labouesse, C. Agley, C. C. Chalut, K. J. Open Biol Research Stem cell fate decisions are driven by a broad array of signals, both chemical and mechanical. Although much progress has been made in our understanding of the impact of chemical signals on cell fate choice, much less is known about the role and influence of mechanical signalling, particularly in embryonic stem (ES) cells. Many studies use substrates with different stiffness to study mechanical signalling, but changing substrate stiffness can induce secondary effects which are difficult to disentangle from the direct effects of forces/mechanical signals. To probe the direct impact of mechanical stress on cells, we developed an adaptable cell substrate stretcher to exert specific, reproducible forces on cells. Using this device to test the response of ES cells to tensile strain, we found that cells experienced a transient influx of calcium followed by an upregulation of the so-called immediate and early genes. On longer time scales, however, ES cells in ground state conditions were largely insensitive to mechanical stress. Nonetheless, as ES cells exited the ground state, their susceptibility to mechanical signals increased, resulting in broad transcriptional changes. Our findings suggest that exit from ground state of pluripotency is unaffected by mechanical signals, but that these signals could become important during the next stage of lineage specification. A better understanding of this process could improve our understanding of cell fate choice in early development and improve protocols for differentiation guided by mechanical cues. The Royal Society 2019-01-09 /pmc/articles/PMC6367133/ /pubmed/30958114 http://dx.doi.org/10.1098/rsob.180203 Text en © 2019 The Authors. http://creativecommons.org/licenses/by/4.0/ Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.
spellingShingle Research
Verstreken, C. M.
Labouesse, C.
Agley, C. C.
Chalut, K. J.
Embryonic stem cells become mechanoresponsive upon exit from ground state of pluripotency
title Embryonic stem cells become mechanoresponsive upon exit from ground state of pluripotency
title_full Embryonic stem cells become mechanoresponsive upon exit from ground state of pluripotency
title_fullStr Embryonic stem cells become mechanoresponsive upon exit from ground state of pluripotency
title_full_unstemmed Embryonic stem cells become mechanoresponsive upon exit from ground state of pluripotency
title_short Embryonic stem cells become mechanoresponsive upon exit from ground state of pluripotency
title_sort embryonic stem cells become mechanoresponsive upon exit from ground state of pluripotency
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6367133/
https://www.ncbi.nlm.nih.gov/pubmed/30958114
http://dx.doi.org/10.1098/rsob.180203
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