Mr The Chinese University of Hong Kong (CUHK) Shatin, Hong Kong
Abstract: Heart diseases are the leading cause of death worldwide. These diseases overwhelm the healthcare systems and exert an enormous economic burden on society. The development of more effective therapeutic strategies for managing and treating heart diseases is militated by knowledge gaps in our understanding of the development and function of the heart. Currently, the broad view of the development and function of the heart is known. However, the nitty-gritty of the processes involved is not known in sufficient detail. For instance, many genes are abundantly expressed in cardiomyocytes, the parenchymal cells of the heart, but their function in cardiomyocytes is largely obscure. Notably, we have found that coiled-coil domain-containing protein141 (CCDC141) is abundantly expressed in cardiomyocytes of vertebrates from the heart development period up to adulthood. To study the function of CCDC141 in cardiomyocyte differentiation, we generated a CCDC141 knockout human embryonic stem cell line (CCDC141-KO hESC) using the clustered regularly interspaced short palindromic repeats (CRISPR) associated protein 9 (CRISPR-Cas9). We further differentiated the CCDC141-KO hESC into cardiomyocytes to examine the effects of loss of CCDC141 in cardiomyocyte development and function. Our results showed that the loss of CCDC141 did not affect the commitment of hESC to cardiomyocyte lineage during in vitro differentiation. The transcriptomic analysis of CCDC141-KO hESC showed altered myofibril and extracellular matrix. Additionally, the loss of CCDC141 function induced the downregulation of genes associated with oxidative phosphorylation with normal mitochondrial abundance. The molecular underpinning of the role of CCDC141 in cardiomyocyte biology is ongoing.
