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Screening identifies small molecules that enhance the maturation of human pluripotent stem cell-derived myotubes.


ABSTRACT: Targeted differentiation of pluripotent stem (PS) cells into myotubes enables in vitro disease modeling of skeletal muscle diseases. Although various protocols achieve myogenic differentiation in vitro, resulting myotubes typically display an embryonic identity. This is a major hurdle for accurately recapitulating disease phenotypes in vitro, as disease commonly manifests at later stages of development. To address this problem, we identified four factors from a small molecule screen whose combinatorial treatment resulted in myotubes with enhanced maturation, as shown by the expression profile of myosin heavy chain isoforms, as well as the upregulation of genes related with muscle contractile function. These molecular changes were confirmed by global chromatin accessibility and transcriptom

SUBMITTER: Selvaraj S 

PROVIDER: S-EPMC6845233 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature