Gene Regulatory Networks in Striated Muscle Pathologies

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2023-05-01T05:00:00.000Z

Authors

Shah, Akansha Mahavir

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Abstract

The striated musculature, comprised of skeletal muscle and cardiac muscle tissues, is essential for vertebrate life. Skeletal muscles are composed of bundles of long and parallel multinucleated myofibers that constitute approximately 40% of the human body mass. The cardiac muscle is much smaller and consists of a branched network of short, mononucleated or binucleated cardiomyocytes that are connected by intercalated discs. Both these tissues partake in force generation through contractile units called sarcomeres to support movement, respiration (skeletal muscle), and to pump oxygenated blood throughout the body (cardiac muscle). Gene regulatory networks, the interactions between lineage or stage-determining transcription factors and the mRNAs they govern, tightly control cell function and striated tissue development and homeostasis. A disruption or change in these complex networks underlies most skeletal and cardiac muscle-related diseases. In this dissertation, we used transcriptomic and epigenomic approaches at single cell or bulk tissue resolution to provide a molecular framework for the function of TWIST2 in rhabdomyosarcoma pathogenesis as well as the mechanisms of heart remodeling and repair following myocardial infarction. In this process, we elucidated critical nodes in complex pathways that can be manipulated to derail the pathological process of FN-RMS or stimulate regeneration and repair in postnatal hearts.

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