Perundurai, D. | Search bioRxiv

bioRxiv2022

Myofiber reconstruction at micron scale reveals longitudinal bands in heart ventricular walls

The coordinated contraction of myocytes drives the heart to beat and circulate blood. Due to the limited spatial resolution of whole heart imaging and the piecemeal nature of high-magnification studies, a confirmed model of myofiber geometry does not yet exist. Using microscopy and computer vision we report the first three-dimensional reconstruction of myofibers across entire mouse ventricular walls at the micron scale, representing a gain of three orders of magnitude in spatial resolution over the existing models. Our analysis reveals prominent longitudinal bands of fibers that are orthogonal to the well-known circumferential ones. Our discovery impacts present understanding of heart wall mechanics and electrical function, with fundamental implications for the study of diseases related to myofiber disorganization.

cell biology↗

bioRxiv2022

Mindin is essential for cutaneous fibrogenesis in a new mouse model of systemic sclerosis

Fibrosis is a result of chronically activated fibroblasts leading to the overproduction of extracellular matrix (ECM), causing tissue hardening and loss of organ function. Systemic sclerosis (SSc) is a fibrotic skin disease marked by inflammation, autoimmunity and vasculopathy along with progressive fibrosis of the skin and internal organs. A major bottleneck in understanding the etiology of SSc has been the lack of a holistic animal model that can mimic the human SSc disease. We found that the transcription factor Snail is overexpressed in the epidermis of SSc patients and a transgenic mouse recapitulating this expression pattern is sufficient to induce hallmark clinical features of the human disease. Using this mouse model as a discovery platform, we have uncovered a critical role for the matricellular protein Mindin in fibrogenesis. Mindin is produced by Snail transgenic skin keratinocytes and aids fibrogenesis by inducing inflammatory cytokine and collagen production in resident dermal fibroblasts. Given the dispensability of Mindin in normal tissue physiology, targeting this protein holds promise as an effective therapy for fibrosis.

pathology↗