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Obesity Impairs Embryonic Myogenesis by Enhancing BMP Signaling within the Dermomyotome

Obesity during pregnancy leads to adverse health outcomes in offspring. However, the initial effects of maternal obesity (MO) on embryonic organogenesis have yet to be thoroughly examined. Using unbiased single‐cell transcriptomic analyses (scRNA‐seq), the effects of MO on the myogenic process is in...

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Autores principales: Zhao, Liang, Law, Nathan C., Gomez, Noe A., Son, Junseok, Gao, Yao, Liu, Xiangdong, de Avila, Jeanene M., Zhu, Mei‐Jun, Du, Min
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8596142/
https://www.ncbi.nlm.nih.gov/pubmed/34647690
http://dx.doi.org/10.1002/advs.202102157
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author Zhao, Liang
Law, Nathan C.
Gomez, Noe A.
Son, Junseok
Gao, Yao
Liu, Xiangdong
de Avila, Jeanene M.
Zhu, Mei‐Jun
Du, Min
author_facet Zhao, Liang
Law, Nathan C.
Gomez, Noe A.
Son, Junseok
Gao, Yao
Liu, Xiangdong
de Avila, Jeanene M.
Zhu, Mei‐Jun
Du, Min
author_sort Zhao, Liang
collection PubMed
description Obesity during pregnancy leads to adverse health outcomes in offspring. However, the initial effects of maternal obesity (MO) on embryonic organogenesis have yet to be thoroughly examined. Using unbiased single‐cell transcriptomic analyses (scRNA‐seq), the effects of MO on the myogenic process is investigated in embryonic day 9.5 (E9.5) mouse embryos. The results suggest that MO induces systematic hypoxia, which is correlated with enhanced BMP signaling and impairs skeletal muscle differentiation within the dermomyotome (DM). The Notch‐signaling effectors, HES1 and HEY1, which also act down‐stream of BMP signaling, suppress myogenic differentiation through transcriptionally repressing the important myogenic regulator MEF2C. Moreover, the major hypoxia effector, HIF1A, enhances expression of HES1 and HEY1 and blocks myogenic differentiation in vitro. In summary, this data demonstrate that MO induces hypoxia and impairs myogenic differentiation by up‐regulating BMP signaling within the DM, which may account for the disruptions of skeletal muscle development and function in progeny.
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spelling pubmed-85961422021-12-02 Obesity Impairs Embryonic Myogenesis by Enhancing BMP Signaling within the Dermomyotome Zhao, Liang Law, Nathan C. Gomez, Noe A. Son, Junseok Gao, Yao Liu, Xiangdong de Avila, Jeanene M. Zhu, Mei‐Jun Du, Min Adv Sci (Weinh) Research Articles Obesity during pregnancy leads to adverse health outcomes in offspring. However, the initial effects of maternal obesity (MO) on embryonic organogenesis have yet to be thoroughly examined. Using unbiased single‐cell transcriptomic analyses (scRNA‐seq), the effects of MO on the myogenic process is investigated in embryonic day 9.5 (E9.5) mouse embryos. The results suggest that MO induces systematic hypoxia, which is correlated with enhanced BMP signaling and impairs skeletal muscle differentiation within the dermomyotome (DM). The Notch‐signaling effectors, HES1 and HEY1, which also act down‐stream of BMP signaling, suppress myogenic differentiation through transcriptionally repressing the important myogenic regulator MEF2C. Moreover, the major hypoxia effector, HIF1A, enhances expression of HES1 and HEY1 and blocks myogenic differentiation in vitro. In summary, this data demonstrate that MO induces hypoxia and impairs myogenic differentiation by up‐regulating BMP signaling within the DM, which may account for the disruptions of skeletal muscle development and function in progeny. John Wiley and Sons Inc. 2021-10-14 /pmc/articles/PMC8596142/ /pubmed/34647690 http://dx.doi.org/10.1002/advs.202102157 Text en © 2021 The Authors. Advanced Science published by Wiley‐VCH GmbH https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Zhao, Liang
Law, Nathan C.
Gomez, Noe A.
Son, Junseok
Gao, Yao
Liu, Xiangdong
de Avila, Jeanene M.
Zhu, Mei‐Jun
Du, Min
Obesity Impairs Embryonic Myogenesis by Enhancing BMP Signaling within the Dermomyotome
title Obesity Impairs Embryonic Myogenesis by Enhancing BMP Signaling within the Dermomyotome
title_full Obesity Impairs Embryonic Myogenesis by Enhancing BMP Signaling within the Dermomyotome
title_fullStr Obesity Impairs Embryonic Myogenesis by Enhancing BMP Signaling within the Dermomyotome
title_full_unstemmed Obesity Impairs Embryonic Myogenesis by Enhancing BMP Signaling within the Dermomyotome
title_short Obesity Impairs Embryonic Myogenesis by Enhancing BMP Signaling within the Dermomyotome
title_sort obesity impairs embryonic myogenesis by enhancing bmp signaling within the dermomyotome
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8596142/
https://www.ncbi.nlm.nih.gov/pubmed/34647690
http://dx.doi.org/10.1002/advs.202102157
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