Gabriela Villalpando Torres
University of California, Santa Barbara
Santa Barbara, CA
Exploring the role of desmin and microtubules in cardiomyocyte remodeling: Insights from an hiPSC-CM model
Gabriella Villalpando Torres, Marissa Gionet-Gonzales, Sam Feinstein
The heart is a dynamic organ that undergoes remodeling during health and disease. Cardiomyocytes, the cells responsible for heart contraction, are composed of both a contractile and a non-contractile cytoskeleton. The contractile cytoskeleton, composed of actin-myosin arrays, generates cell contraction. Recent work has shown that the non-contractile cytoskeleton, specifically desmin and microtubules, form a network that resists contraction and provides support to the cardiomyocyte. Microtubule and desmin protein expression has been shown to increase in diseases such as Hypertrophic Cardiomyopathy (HCM), a disease associated with stiffening of the heart wall as well as increased cell size and force production. Although this has been consistently observed, the mechanism behind this increase remains unknown. To probe this mechanism, we use human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) as a model. We modulate hiPSC-CM force production in three ways: by culturing on hydrogels of increasing stiffness, treatment with contractility-altering drugs, and introducing an HCM mutation to enhance contractility. We hypothesize that increased force production under pathophysiological conditions leads to higher desmin and microtubule protein expression. Bulk RNA-seq data reveals that enhancing contractility with drugs in control hiPSC-CMs increases expression of desmin and various tubulin isoforms. At the protein level, a slight increase in microtubule network density is noted with increasing stiffness, as observed through immunofluorescence. Additionally, we observe that desmin content varies among hiPSC-CMs, with not all cells testing positive for it. These results provide insight into how cardiomyocytes adapt to pathophysiological conditions and highlight limitations in using iPSC-CMs as a model.
SACNAS National Diversity in STEM Conference, Phoenix, AZ, October 30-November 2, 2024
