Genomics and epigenomics of tissue repair: Implications for personalized medicine

Abstract

The healing of tissues is a highly coordinated development process which includes cell proliferation and differentiation, immune modulation, and extracellular‐matrix remodeling. Genetic variation, which encompasses single‐nucleotide polymorphisms (SNPs) and copy‐number variations (CNVs), and epigenetic corrections such as DNA methylation, post‐translational changes to histones, and non‐coding RNA activity might impact regenerative capacity and individual response to injury. High‐throughput sequencing and molecular profiling technologies have made it feasible to conduct genome and epigenome‐wide studies, clarifying how genomic and epigenomic contributions impact reparative processes. For example, certain SNPs may alter signaling pathways that induce tissue growth and, likewise, epigenetic changes may alter gene‐expression patterns following injury that may affect healing. Furthermore, combining genomic and epigenomic data will allow for the development of therapies specific to an individual's capacity for repair and susceptibility for scarring. While biomarker discovery, the identification of molecular features that correlate with the efficiency of healing and/or responsiveness to treatment, would additionally provide a tangible example of precision regenerative medicine. Regenerative strategies targeting a genetic mutation or secondarily changing the epigenome to promote tissue healing would provide an opportunity to improve healing outcomes by connecting molecular mechanisms to therapeutic interventions, which would enhance regeneration while also minimizing fibrosis and other unwanted effects.