Chemical reprogramming of melanocytes to skeletal muscle cells

Abstract Background Direct cell‐fate conversion by chemical reprogramming is promising for regenerative cell therapies. However, this process requires the reactivation of a set of master transcription factors (TFs) of the target cell type, which has proven challenging using only small molecules. Methods We developed a novel small‐molecule cocktail permitting robust skin cell to muscle cell conversion. By single cell sequencing analysis, we identified a Pax3 (Paired box 3)‐expressing melanocyte population holding a superior myogenic potential outperforming other seven types of skin cells. We further validated the single cell sequencing analysis results using immunofluorescence staining, in situ hybridization and FACS sorting and confirmed the myogenic potential of melanocytes during chemical reprogramming. We used single cell RNA‐seq that detect the potential converted cell type, uncovering a unique role of Pax3 in facilitating chemical reprogramming from melanocytes to muscle cells. Results In this study, we demonstrated that the Pax3‐expressing melanocytes to be a skin cell type for skeletal muscle cell fate conversion in chemical reprogramming. By developing a small‐molecule cocktail, we showed an efficient melanocyte reprogramming to skeletal muscle cells (40%, P < 0.001). The endogenous expression of specific TFs may circumvent the additional requirement for TF reactivation and form a shortcut for cell fate conversion, suggesting a basic principle that could ease cell fate conversion. Conclusions Our study demonstrates the first report of melanocyte‐to‐muscle conversion by small molecules, suggesting a novel strategy for muscle regeneration. Furthermore, skin is one of the tissues closely located to skeletal muscle, and therefore, our results provide a promising foundation for therapeutic chemical reprogramming in vivo treating skeletal muscle degenerative diseases

Mid-Infrared Hollow-Core Fiber Based Flexible Longitudinal Photoacoustic Resonator for Photoacoustic Spectroscopy Gas Sensing

Photoacoustic spectroscopy (PAS) has received extensive attention in optical gas sensing due to the advantages of high sensitivity, gas selectivity, and online detection. Here, a mid-infrared hollow-core fiber (HCF) based flexible longitudinal photoacoustic resonator for PAS-based gas sensing is proposed and theoretically demonstrated. A mid-infrared anti-resonant HCF is designed to innovatively replace the traditional metallic acoustic resonator and obtain a flexible photoacoustic cell in PAS. Optical transmission characteristics of the HCF are analyzed and discussed, achieving single mode operation with below 1 dB/m confinement loss between 3 and 8 μm and covering strong absorptions of some hydrocarbons and carbon oxides. With varied bending radii from 10 mm to 200 mm, the optical mode could be maintained in the hollow core. Based on the photoacoustic effect, generated acoustic mode distributions in the HCF-based flexible photoacoustic resonator are analyzed and compared. Results show that the PAS-based sensor has a stable and converged acoustic profile at the resonant frequency of around 16,787 Hz and a favorable linear response to light source power and gas concentration. The proposed novel photoacoustic resonator using HCF presents bring potential for advanced flexible PAS-based gas detection

LONGITUDINAL CHANGES IN CHOROIDAL AND RETINAL THICKNESSES IN CHILDREN WITH MYOPIC SHIFT

Axial length elongation and choroidal thinning are independently associated with myopic shift. Choroidal thinning precedes retinal thinning in the early stage of myopic progression

The asymmetrical ESR1 signaling in muscle progenitor cells determines the progression of adolescent idiopathic scoliosis

Abstract Adolescent Idiopathic Scoliosis (AIS) is a common pediatric skeletal disease highly occurred in females. The pathogenesis of AIS has not been fully elucidated. Here, we reveal that ESR1 (Estrogen Receptor 1) expression declines in muscle stem/progenitor cells at the concave side of AIS patients. Furthermore, ESR1 is required for muscle stem/progenitor cell differentiation and disrupted ESR1 signaling leads to differentiation defects. The imbalance of ESR1 signaling in the para-spinal muscles induces scoliosis in mice, while reactivation of ESR1 signaling at the concave side by an FDA approved drug Raloxifene alleviates the curve progression. This work reveals that the asymmetric inactivation of ESR1 signaling is one of the causes of AIS. Reactivation of ESR1 signaling in para-spinal muscle by Raloxifene at the concave side could be a new strategy to treat AIS