Posters

Discipline Track

Biomedical ENGR/Technology/Computation

Abstract

Advances in iPSC technologies now allow us to consider non-invasive large-scale in-vitro disease modeling experiments on disease appropriate cell types in human subjects to better understand human disease pathophysiology, disease genetics and to develop better diagnostic and therapeutic technologies. We performed differential gene expression and functional annotation analysis using genome wide mRNA sequencing data to evaluate the functional and disease modeling potential of iPSC generated hepatocytes. Following the criteria moderated t statistics FDR corrected p-value ≤ 0.05 and fold change-absolute ≥ 2.0, 7,246 genes/transcripts were significantly differentially expressed iPSCs and hepatocytes. The 3,791 of these DE genes/transcripts were significantly upregulated in the hepatocytes and accounted for about 55% of the hepatocytes total expressed transcriptome. The heatmap and principal component analysis suggests a discrete and uniform resetting of cellular transcriptome during iPSC to hepatocyte differentiation. The functional annotation analysis of the 3,791 significantly upregulated hepatocytes genes/transcripts showed significant enrichment hepatocytes associated cellular functions and canonical pathways. The gene known to be associated with various common human liver disorders and toxicities were also significantly enriched in hepatocytes upregulated 3,791 genes/transcripts. These results suggest that iPSC generated hepatocytes have a functional profile very similar to human primary hepatocytes and are suitable for in-vitro modeling of human liver disorders and toxicities.

Presentation Type

Poster

Academic Level

Medical Student

Mentor/PI Department

Office of Human Genetics

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Functional characterization of the iPSC generated hepatocytes using genome-wide transcriptomic analysis

Advances in iPSC technologies now allow us to consider non-invasive large-scale in-vitro disease modeling experiments on disease appropriate cell types in human subjects to better understand human disease pathophysiology, disease genetics and to develop better diagnostic and therapeutic technologies. We performed differential gene expression and functional annotation analysis using genome wide mRNA sequencing data to evaluate the functional and disease modeling potential of iPSC generated hepatocytes. Following the criteria moderated t statistics FDR corrected p-value ≤ 0.05 and fold change-absolute ≥ 2.0, 7,246 genes/transcripts were significantly differentially expressed iPSCs and hepatocytes. The 3,791 of these DE genes/transcripts were significantly upregulated in the hepatocytes and accounted for about 55% of the hepatocytes total expressed transcriptome. The heatmap and principal component analysis suggests a discrete and uniform resetting of cellular transcriptome during iPSC to hepatocyte differentiation. The functional annotation analysis of the 3,791 significantly upregulated hepatocytes genes/transcripts showed significant enrichment hepatocytes associated cellular functions and canonical pathways. The gene known to be associated with various common human liver disorders and toxicities were also significantly enriched in hepatocytes upregulated 3,791 genes/transcripts. These results suggest that iPSC generated hepatocytes have a functional profile very similar to human primary hepatocytes and are suitable for in-vitro modeling of human liver disorders and toxicities.

 

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