From gene expression to function – a pipeline for manipulating and characterizing human iPSC-cardiomyocytes
Animal models, especially transgenic rodent models, have enhanced our understanding of cardiovascular function at the molecular level. Yet, they come with some limitations in their relevance to human health and the suitability to assess personalized responses to treatment. In this talk, several technological approaches will be outlined to illustrate how we can build a pipeline for manipulating and characterizing human stem-cell-derived cardiomyocytes (iPSC-CMs) in a high-throughput manner. The methodology involves cell-specific gene modulation techniques, non-contact optical methods for functional analysis coupled with microfluidics and with newer scalable gene and protein quantification methods. The pipeline opens the door for functional genomics with human iPSC-CMs by offering correlative analysis between phenotype and molecular underpinnings. Our analysis of gene regulation based on next generation sequencing in adult human hearts vs. human iPSC-CMs reinforces the utility of the latter as an experimental model. These efforts contribute to building a compelling framework for testing pharmacological and gene therapies for personalized medicine.
