Obesity Impairs Embryonic Myogenesis by Enhancing BMP Signaling within the Dermomyotome.
Liang ZhaoNathan C LawNoe A GomezJunseok SonYao GaoXiangdong LiuJeanene M de AvilaMei-Jun ZhuMin DuPublished in: Advanced science (Weinheim, Baden-Wurttemberg, Germany) (2021)
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.
Keyphrases
- skeletal muscle
- insulin resistance
- single cell
- mesenchymal stem cells
- metabolic syndrome
- high fat diet
- endothelial cells
- weight loss
- high fat diet induced
- type diabetes
- rna seq
- weight gain
- bone regeneration
- poor prognosis
- adipose tissue
- glycemic control
- physical activity
- genome wide
- regulatory t cells
- emergency department
- gene expression
- body mass index
- immune response
- high throughput
- dna methylation
- atomic force microscopy
- single molecule
- deep learning
- high speed