BMP Signaling Determines the Proximodistal Pattern of Limb Muscles by Spatiotemporal Control of Myogenic Progenitor Cells

2021 ◽  
Author(s):  
Hasan Asfour ◽  
Estelle Hirsinger ◽  
Raquel Rouco ◽  
Faouzi Zarrouki ◽  
Arunima Murgai ◽  
...  
2017 ◽  
Vol 93 ◽  
pp. 15-26 ◽  
Author(s):  
Vincent Grassot ◽  
Amel Bouchatal ◽  
Anne Da Silva ◽  
Sandrine Chantepie ◽  
Dulce Papy-Garcia ◽  
...  

2021 ◽  
Author(s):  
Inseon Kim ◽  
Adhideb Ghosh ◽  
Nicola Bundschuh ◽  
Laura Hinte ◽  
Ferdinand von Meyenn ◽  
...  

Transient MyoD overexpression in concert with small molecules treatment reprograms mouse fibroblasts into induced myogenic progenitor cells (iMPCs). However, the molecular landscape and mechanisms orchestrating this cellular conversion remain unknown. Here, we undertook an integrative multi-omics approach to delineate the process of iMPC reprogramming in comparison to myogenic transdifferentiation mediated solely by MyoD. Utilizing transcriptomics, proteomics and genome-wide chromatin accessibility assays, we unravel distinct molecular trajectories which govern the two processes. Notably, iMPC reprogramming is characterized by gradual upregulation of stem and progenitor cell markers, unique signaling pathways, chromatin remodelers and cell cycle regulators which manifest via rewiring of the chromatin in core myogenic promoters. Furthermore, we determine that only iMPC reprogramming is mediated by Notch pathway activation, which is indispensable for iMPC formation and self-renewal. Collectively, this study charts divergent molecular blueprints for myogenic transdifferentiation or reprogramming and underpins the heightened capacity of iMPCs in capturing myogenesis ex vivo.


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