Zyxin regulates embryonic stem cell fate by modulating mechanical and biochemical signaling interface
Biochemical signaling and mechano-transduction are both critical in regulating stem cell fate. How crosstalk between mechanical and biochemical cues influences embryonic development, however, is not extensively investigated. Using a comparative study of focal adhesion constituents between mouse embr...
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sg-ntu-dr.10356-1687692023-10-13T06:05:35Z Zyxin regulates embryonic stem cell fate by modulating mechanical and biochemical signaling interface Zhang, Songjing Chong, Lor Huai Woon, Jessie Yong Xing Chua, Theng Xuan Cheruba, Elsie Yip, Ai Kia Li, Hoi-Yeung Chiam, Keng-Hwee Koh, Cheng-Gee School of Biological Sciences Science::Biological sciences::Molecular biology Embryonic Stem Cell Focal Adhesion Biochemical signaling and mechano-transduction are both critical in regulating stem cell fate. How crosstalk between mechanical and biochemical cues influences embryonic development, however, is not extensively investigated. Using a comparative study of focal adhesion constituents between mouse embryonic stem cell (mESC) and their differentiated counterparts, we find while zyxin is lowly expressed in mESCs, its levels increase dramatically during early differentiation. Interestingly, overexpression of zyxin in mESCs suppresses Oct4 and Nanog. Using an integrative biochemical and biophysical approach, we demonstrate involvement of zyxin in regulating pluripotency through actin stress fibres and focal adhesions which are known to modulate cellular traction stress and facilitate substrate rigidity-sensing. YAP signaling is identified as an important biochemical effector of zyxin-induced mechanotransduction. These results provide insights into the role of zyxin in the integration of mechanical and biochemical cues for the regulation of embryonic stem cell fate. Ministry of Education (MOE) Nanyang Technological University Published version We thank Singapore Ministry of Education MOE Tier 2 grant (MOE2018-T2-1-058), MOE Tier 1 grant (RG106/20) and Nanyang Technological University, Singapore SUG grant to C.G.K. for funding support. 2023-06-19T04:50:06Z 2023-06-19T04:50:06Z 2023 Journal Article Zhang, S., Chong, L. H., Woon, J. Y. X., Chua, T. X., Cheruba, E., Yip, A. K., Li, H., Chiam, K. & Koh, C. (2023). Zyxin regulates embryonic stem cell fate by modulating mechanical and biochemical signaling interface. Communications Biology, 6(1), 62-. https://dx.doi.org/10.1038/s42003-023-04421-0 2399-3642 https://hdl.handle.net/10356/168769 10.1038/s42003-023-04421-0 36653484 2-s2.0-85146486019 1 6 62 en MOE2018-T2-1-058 RG106/20 NTU-SUG Communications Biology 10.21979/N9/YKONJT © 2023 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/. application/pdf |
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Science::Biological sciences::Molecular biology Embryonic Stem Cell Focal Adhesion Zhang, Songjing Chong, Lor Huai Woon, Jessie Yong Xing Chua, Theng Xuan Cheruba, Elsie Yip, Ai Kia Li, Hoi-Yeung Chiam, Keng-Hwee Koh, Cheng-Gee Zyxin regulates embryonic stem cell fate by modulating mechanical and biochemical signaling interface |
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Biochemical signaling and mechano-transduction are both critical in regulating stem cell fate. How crosstalk between mechanical and biochemical cues influences embryonic development, however, is not extensively investigated. Using a comparative study of focal adhesion constituents between mouse embryonic stem cell (mESC) and their differentiated counterparts, we find while zyxin is lowly expressed in mESCs, its levels increase dramatically during early differentiation. Interestingly, overexpression of zyxin in mESCs suppresses Oct4 and Nanog. Using an integrative biochemical and biophysical approach, we demonstrate involvement of zyxin in regulating pluripotency through actin stress fibres and focal adhesions which are known to modulate cellular traction stress and facilitate substrate rigidity-sensing. YAP signaling is identified as an important biochemical effector of zyxin-induced mechanotransduction. These results provide insights into the role of zyxin in the integration of mechanical and biochemical cues for the regulation of embryonic stem cell fate. |
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School of Biological Sciences |
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School of Biological Sciences Zhang, Songjing Chong, Lor Huai Woon, Jessie Yong Xing Chua, Theng Xuan Cheruba, Elsie Yip, Ai Kia Li, Hoi-Yeung Chiam, Keng-Hwee Koh, Cheng-Gee |
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Article |
author |
Zhang, Songjing Chong, Lor Huai Woon, Jessie Yong Xing Chua, Theng Xuan Cheruba, Elsie Yip, Ai Kia Li, Hoi-Yeung Chiam, Keng-Hwee Koh, Cheng-Gee |
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Zhang, Songjing |
title |
Zyxin regulates embryonic stem cell fate by modulating mechanical and biochemical signaling interface |
title_short |
Zyxin regulates embryonic stem cell fate by modulating mechanical and biochemical signaling interface |
title_full |
Zyxin regulates embryonic stem cell fate by modulating mechanical and biochemical signaling interface |
title_fullStr |
Zyxin regulates embryonic stem cell fate by modulating mechanical and biochemical signaling interface |
title_full_unstemmed |
Zyxin regulates embryonic stem cell fate by modulating mechanical and biochemical signaling interface |
title_sort |
zyxin regulates embryonic stem cell fate by modulating mechanical and biochemical signaling interface |
publishDate |
2023 |
url |
https://hdl.handle.net/10356/168769 |
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1781793695237931008 |