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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Main Authors: 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
Other Authors: School of Biological Sciences
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Language:English
Published: 2023
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Online Access:https://hdl.handle.net/10356/168769
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Institution: Nanyang Technological University
Language: English
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spelling 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
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Science::Biological sciences::Molecular biology
Embryonic Stem Cell
Focal Adhesion
spellingShingle 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
description 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.
author2 School of Biological Sciences
author_facet 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
format 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
author_sort 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
_version_ 1781793695237931008