Project description:Enhancing the proliferation and myogenic commitment of progenitor cells during fetal development enhances muscle growth and lean production in offspring. During the early development, a pool of skeletal stem cells (SSCs) proliferates and then diverge into either myoblast. Myoblast further fusion and develop into myotube. However, the landscape from muscle stem cells to myotubes in goats is not yet clear. This study aims to characterize the changes in the expression profile of skeletal muscle stem cells that differentiate into myoblasts, then migrate and fuse to form myotubes.
Project description:Direct lineage reprogramming provides a unique system to study cell fate transitions and unearth molecular mechanisms that safeguard cellular identity. We previously reported on direct conversion of mouse fibroblasts into induced myogenic progenitor cells (iMPCs) by transient MyoD overexpression in concert with small molecules treatment. Here we employed integrative multi-omic approaches to delineate the molecular landscape of fibroblast reprogramming into iMPCs in comparison to transdifferentiation into myogenic cells solely by MyoD overexpression. Utilizing bulk RNA-sequencing and mass spectrometry, we uncovered molecular regulators and pathways that endow a myogenic stem cell identity on fibroblasts only in the presence of small molecule treatment. In addition, we demonstrate that Pax7+ cells in iMPCs share molecular attributes with myoblasts, however in addition express unique genes, proteins and pathways that are indicative of a more activated satellite cell-like state in vitro. Collectively, this study charts a molecular blueprint for reprogramming fibroblasts into muscle stem and progenitor cells and further establishes the fidelity of stable iMPC cultures in capturing skeletal muscle regeneration in vitro for disease modeling and basic research applications.
Project description:Adult muscle stem cells, also known as muscle satellite cells, which are the resident tissue stem cells of skeletal muscle, provide myonuclei for postnatal muscle growth and for maintenance and regeneration in adults. Satellite cells specifically express the transcription factor pax7. The purpose of this study was to identify pax7 target genes and clarify the role of pax7 in muscle stem cell maintenance. We succeeded in generating Pax7-YFP knockin mice (Pax7-YFP KI) that can visualize endogenous pax7 expressed in satellite cells with YFP fluorescent protein. Novel pax7 target genes were identified by ChIP-sequencing (chromatin immunoprecipitation) analysis with muscle stem cells of Pax7-YFP KI mice.
Project description:We report mitochondrial genome (mtDNA) sequences in purified mouse muscle stem cells at different ages. This study identifies changes in the mitochondrial genome of muscle stem cells during aging.
