Obesity Impairs Embryonic Myogenesis by Enhancing BMP Signaling within the Dermomyotome
| Autor: | Min Du, Yao Gao, Jeanene M. de Avila, Junseok Son, Noe Alberto Gomez, Nathan C. Law, Mei-Jun Zhu, Xiangdong Liu, Liang Zhao |
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| Rok vydání: | 2021 |
| Předmět: |
General Chemical Engineering
Science General Physics and Astronomy Medicine (miscellaneous) Dermomyotome Biology Muscle Development Biochemistry Genetics and Molecular Biology (miscellaneous) Transcriptome Obesity Maternal Mice Pregnancy embryonic myogenesis single cell RNA sequencing medicine Animals General Materials Science MEF2C HES1 Research Articles bone morphogenetic proteins signaling Myogenesis General Engineering Skeletal muscle Cell Differentiation Embryonic stem cell Cell biology Mice Inbred C57BL Pregnancy Complications maternal obesity Disease Models Animal HIF1A medicine.anatomical_structure Bone Morphogenetic Proteins Female Signal Transduction Research Article |
| Zdroj: | Advanced Science Advanced Science, Vol 8, Iss 22, Pp n/a-n/a (2021) |
| ISSN: | 2198-3844 |
| Popis: | 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. Molecular mechanisms controlling embryonic myogenesis are examined by a pseudo temporal model at the single‐cell level. Moreover, maternal obesity attenuates myogenic differentiation in E9.5 embryos by enhancing bone morphogenetic protein (BMP) signaling within the dermomyotome, which suppresses Mef2c expression. Disrupted embryonic myogenesis provides a mechanistic explanation for the impairments in muscle function of offspring due to maternal obesity. |
| Databáze: | OpenAIRE |
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