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Thyroid hormone enhances stem cell maintenance and promotes lineage-specific differentiation in human embryonic stem cells

BACKGROUND: Thyroid hormone triiodothyronine (T3) is essential for embryogenesis and is commonly used during in vitro fertilization to ensure successful implantation. However, the regulatory mechanisms of T3 during early embryogenesis are largely unknown. METHOD: To study the impact of T3 on hPSCs,...

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Autores principales: Deng, Chunhao, Zhang, Zhaoying, Xu, Faxiang, Xu, Jiaqi, Ren, Zhili, Godoy-Parejo, Carlos, Xiao, Xia, Liu, Weiwei, Zhou, Zhou, Chen, Guokai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8935725/
https://www.ncbi.nlm.nih.gov/pubmed/35313973
http://dx.doi.org/10.1186/s13287-022-02799-y
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author Deng, Chunhao
Zhang, Zhaoying
Xu, Faxiang
Xu, Jiaqi
Ren, Zhili
Godoy-Parejo, Carlos
Xiao, Xia
Liu, Weiwei
Zhou, Zhou
Chen, Guokai
author_facet Deng, Chunhao
Zhang, Zhaoying
Xu, Faxiang
Xu, Jiaqi
Ren, Zhili
Godoy-Parejo, Carlos
Xiao, Xia
Liu, Weiwei
Zhou, Zhou
Chen, Guokai
author_sort Deng, Chunhao
collection PubMed
description BACKGROUND: Thyroid hormone triiodothyronine (T3) is essential for embryogenesis and is commonly used during in vitro fertilization to ensure successful implantation. However, the regulatory mechanisms of T3 during early embryogenesis are largely unknown. METHOD: To study the impact of T3 on hPSCs, cell survival and growth were evaluated by measurement of cell growth curve, cloning efficiency, survival after passaging, cell apoptosis, and cell cycle status. Pluripotency was evaluated by RT-qPCR, immunostaining and FACS analysis of pluripotency markers. Metabolic status was analyzed using LC–MS/MS and Seahorse XF Cell Mito Stress Test. Global gene expression was analyzed using RNA-seq. To study the impact of T3 on lineage-specific differentiation, cells were subjected to T3 treatment during differentiation, and the outcome was evaluated using RT-qPCR, immunostaining and FACS analysis of lineage-specific markers. RESULTS: In this report, we use human pluripotent stem cells (hPSCs) to show that T3 is beneficial for stem cell maintenance and promotes trophoblast differentiation. T3 enhances culture consistency by improving cell survival and passaging efficiency. It also modulates cellular metabolism and promotes energy production through oxidative phosphorylation. T3 helps maintain pluripotency by promoting ERK and SMAD2 signaling and reduces FGF2 dependence in chemically defined culture. Under BMP4 induction, T3 significantly enhances trophoblast differentiation. CONCLUSION: In summary, our study reveals the impact of T3 on stem cell culture through signal transduction and metabolism and highlights its potential role in improving stem cell applications. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13287-022-02799-y.
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spelling pubmed-89357252022-03-23 Thyroid hormone enhances stem cell maintenance and promotes lineage-specific differentiation in human embryonic stem cells Deng, Chunhao Zhang, Zhaoying Xu, Faxiang Xu, Jiaqi Ren, Zhili Godoy-Parejo, Carlos Xiao, Xia Liu, Weiwei Zhou, Zhou Chen, Guokai Stem Cell Res Ther Research BACKGROUND: Thyroid hormone triiodothyronine (T3) is essential for embryogenesis and is commonly used during in vitro fertilization to ensure successful implantation. However, the regulatory mechanisms of T3 during early embryogenesis are largely unknown. METHOD: To study the impact of T3 on hPSCs, cell survival and growth were evaluated by measurement of cell growth curve, cloning efficiency, survival after passaging, cell apoptosis, and cell cycle status. Pluripotency was evaluated by RT-qPCR, immunostaining and FACS analysis of pluripotency markers. Metabolic status was analyzed using LC–MS/MS and Seahorse XF Cell Mito Stress Test. Global gene expression was analyzed using RNA-seq. To study the impact of T3 on lineage-specific differentiation, cells were subjected to T3 treatment during differentiation, and the outcome was evaluated using RT-qPCR, immunostaining and FACS analysis of lineage-specific markers. RESULTS: In this report, we use human pluripotent stem cells (hPSCs) to show that T3 is beneficial for stem cell maintenance and promotes trophoblast differentiation. T3 enhances culture consistency by improving cell survival and passaging efficiency. It also modulates cellular metabolism and promotes energy production through oxidative phosphorylation. T3 helps maintain pluripotency by promoting ERK and SMAD2 signaling and reduces FGF2 dependence in chemically defined culture. Under BMP4 induction, T3 significantly enhances trophoblast differentiation. CONCLUSION: In summary, our study reveals the impact of T3 on stem cell culture through signal transduction and metabolism and highlights its potential role in improving stem cell applications. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13287-022-02799-y. BioMed Central 2022-03-21 /pmc/articles/PMC8935725/ /pubmed/35313973 http://dx.doi.org/10.1186/s13287-022-02799-y Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Deng, Chunhao
Zhang, Zhaoying
Xu, Faxiang
Xu, Jiaqi
Ren, Zhili
Godoy-Parejo, Carlos
Xiao, Xia
Liu, Weiwei
Zhou, Zhou
Chen, Guokai
Thyroid hormone enhances stem cell maintenance and promotes lineage-specific differentiation in human embryonic stem cells
title Thyroid hormone enhances stem cell maintenance and promotes lineage-specific differentiation in human embryonic stem cells
title_full Thyroid hormone enhances stem cell maintenance and promotes lineage-specific differentiation in human embryonic stem cells
title_fullStr Thyroid hormone enhances stem cell maintenance and promotes lineage-specific differentiation in human embryonic stem cells
title_full_unstemmed Thyroid hormone enhances stem cell maintenance and promotes lineage-specific differentiation in human embryonic stem cells
title_short Thyroid hormone enhances stem cell maintenance and promotes lineage-specific differentiation in human embryonic stem cells
title_sort thyroid hormone enhances stem cell maintenance and promotes lineage-specific differentiation in human embryonic stem cells
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8935725/
https://www.ncbi.nlm.nih.gov/pubmed/35313973
http://dx.doi.org/10.1186/s13287-022-02799-y
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