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Tenogenic Induction From Induced Pluripotent Stem Cells Unveils the Trajectory Towards Tenocyte Differentiation

The musculoskeletal system is integrated by tendons that are characterized by the expression of scleraxis (Scx), a functionally important transcription factor. Here, we newly developed a tenocyte induction method using induced pluripotent stem cells established from ScxGFP transgenic mice by monitor...

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Autores principales: Yoshimoto, Yuki, Uezumi, Akiyoshi, Ikemoto-Uezumi, Madoka, Tanaka, Kaori, Yu, Xinyi, Kurosawa, Tamaki, Yambe, Shinsei, Maehara, Kazumitsu, Ohkawa, Yasuyuki, Sotomaru, Yusuke, Shukunami, Chisa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8965463/
https://www.ncbi.nlm.nih.gov/pubmed/35372337
http://dx.doi.org/10.3389/fcell.2022.780038
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author Yoshimoto, Yuki
Uezumi, Akiyoshi
Ikemoto-Uezumi, Madoka
Tanaka, Kaori
Yu, Xinyi
Kurosawa, Tamaki
Yambe, Shinsei
Maehara, Kazumitsu
Ohkawa, Yasuyuki
Sotomaru, Yusuke
Shukunami, Chisa
author_facet Yoshimoto, Yuki
Uezumi, Akiyoshi
Ikemoto-Uezumi, Madoka
Tanaka, Kaori
Yu, Xinyi
Kurosawa, Tamaki
Yambe, Shinsei
Maehara, Kazumitsu
Ohkawa, Yasuyuki
Sotomaru, Yusuke
Shukunami, Chisa
author_sort Yoshimoto, Yuki
collection PubMed
description The musculoskeletal system is integrated by tendons that are characterized by the expression of scleraxis (Scx), a functionally important transcription factor. Here, we newly developed a tenocyte induction method using induced pluripotent stem cells established from ScxGFP transgenic mice by monitoring fluorescence, which reflects a dynamic differentiation process. Among several developmentally relevant factors, transforming growth factor-beta 2 (TGF-β2) was the most potent inducer for differentiation of tenomodulin-expressing mature tenocytes. Single-cell RNA sequencing (scRNA-seq) revealed 11 distinct clusters, including mature tenocyte population and tenogenic differentiation trajectory, which recapitulated the in vivo developmental process. Analysis of the scRNA-seq dataset highlighted the importance of retinoic acid (RA) as a regulatory pathway of tenogenic differentiation. RA signaling was shown to have inhibitory effects on entheseal chondrogenic differentiation as well as TGF-β2-dependent tenogenic/fibrochondrogenic differentiation. The collective findings provide a new opportunity for tendon research and further insight into the mechanistic understanding of the differentiation pathway to a tenogenic fate.
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spelling pubmed-89654632022-03-31 Tenogenic Induction From Induced Pluripotent Stem Cells Unveils the Trajectory Towards Tenocyte Differentiation Yoshimoto, Yuki Uezumi, Akiyoshi Ikemoto-Uezumi, Madoka Tanaka, Kaori Yu, Xinyi Kurosawa, Tamaki Yambe, Shinsei Maehara, Kazumitsu Ohkawa, Yasuyuki Sotomaru, Yusuke Shukunami, Chisa Front Cell Dev Biol Cell and Developmental Biology The musculoskeletal system is integrated by tendons that are characterized by the expression of scleraxis (Scx), a functionally important transcription factor. Here, we newly developed a tenocyte induction method using induced pluripotent stem cells established from ScxGFP transgenic mice by monitoring fluorescence, which reflects a dynamic differentiation process. Among several developmentally relevant factors, transforming growth factor-beta 2 (TGF-β2) was the most potent inducer for differentiation of tenomodulin-expressing mature tenocytes. Single-cell RNA sequencing (scRNA-seq) revealed 11 distinct clusters, including mature tenocyte population and tenogenic differentiation trajectory, which recapitulated the in vivo developmental process. Analysis of the scRNA-seq dataset highlighted the importance of retinoic acid (RA) as a regulatory pathway of tenogenic differentiation. RA signaling was shown to have inhibitory effects on entheseal chondrogenic differentiation as well as TGF-β2-dependent tenogenic/fibrochondrogenic differentiation. The collective findings provide a new opportunity for tendon research and further insight into the mechanistic understanding of the differentiation pathway to a tenogenic fate. Frontiers Media S.A. 2022-03-09 /pmc/articles/PMC8965463/ /pubmed/35372337 http://dx.doi.org/10.3389/fcell.2022.780038 Text en Copyright © 2022 Yoshimoto, Uezumi, Ikemoto-Uezumi, Tanaka, Yu, Kurosawa, Yambe, Maehara, Ohkawa, Sotomaru and Shukunami. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Yoshimoto, Yuki
Uezumi, Akiyoshi
Ikemoto-Uezumi, Madoka
Tanaka, Kaori
Yu, Xinyi
Kurosawa, Tamaki
Yambe, Shinsei
Maehara, Kazumitsu
Ohkawa, Yasuyuki
Sotomaru, Yusuke
Shukunami, Chisa
Tenogenic Induction From Induced Pluripotent Stem Cells Unveils the Trajectory Towards Tenocyte Differentiation
title Tenogenic Induction From Induced Pluripotent Stem Cells Unveils the Trajectory Towards Tenocyte Differentiation
title_full Tenogenic Induction From Induced Pluripotent Stem Cells Unveils the Trajectory Towards Tenocyte Differentiation
title_fullStr Tenogenic Induction From Induced Pluripotent Stem Cells Unveils the Trajectory Towards Tenocyte Differentiation
title_full_unstemmed Tenogenic Induction From Induced Pluripotent Stem Cells Unveils the Trajectory Towards Tenocyte Differentiation
title_short Tenogenic Induction From Induced Pluripotent Stem Cells Unveils the Trajectory Towards Tenocyte Differentiation
title_sort tenogenic induction from induced pluripotent stem cells unveils the trajectory towards tenocyte differentiation
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8965463/
https://www.ncbi.nlm.nih.gov/pubmed/35372337
http://dx.doi.org/10.3389/fcell.2022.780038
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