Mechanisms of cellular reprogramming
Investigating the mechanisms governing direct reprogramming in the myogenic lineage
Direct lineage reprogramming represents the transformation of one cell type into another, commonly achieved by the overexpression of defined transcription factors or treatment with small molecules. Our research group, alongside others, has reported that overexpression of the transcription factor MyoD in concert with 3 small molecules, induces the conversion of connective tissue cells termed fibroblasts into induced myogenic progenitor cells (iMPCs). These iMPCs can be extensively expanded in vitro and contribute to muscle regeneration in vivo (external pageBar-Nur et al., Stem Cell Reports, 2018). This observation is distinct from the classical discovery that MyoD overexpression alone generates non-proliferative postmitotic myotubes (Davis et al., Cell, 1987). This phenomenon raises an interesting question: how do small molecules that affect signaling pathways facilitate a stem cell fate versus a postmitotic cell-fate conversion in vitro? To explore this question, we employ a suite of molecular biology techniques to unravel how this rewiring of cellular identity occurs. One primary focus includes utilizing multiomics approaches to dissect the somatic cell reprogramming process into myogenic stem, progenitor and differentiated cells (external pageKim et al., Science Advances, 2022). Our ongoing current endeavors involve employing various molecular biology and transgenic tools to understand the conversion of fibroblasts into iMPCs, in addition to analyzing the various cell populations that comprise iMPC cultures, aiming to assess how faithfully they recapitulate muscle regeneration in vivo. Additionally, an ongoing effort in our lab is dedicated to generating human iMPCs through a similar direct reprogramming approach, with implication extending to both basic research and translational applications.
