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Stem Cell Hub, California Institute for Regenerative Medicine CESCG at UC Santa Cruz

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Snyder Lab: Genomic and transcriptomic analysis of HCM and DCM using iPSC-derived cardiomyoyctes both with and without drug treatment

Lab information [ Lab website | CIRM grants ]

Experimental design

Flowchart

Summary

Heart failure is a very common and chronic condition characterized by insufficient blood supply due to pump dysfunction. Heart failure has a high mortality rate of 50% in 5 years. One of the most common causes of heart failure is cardiomyopathy, most of which is thought to have an identifiable genetic cause. Nonetheless, the majority of the cases of cardiomyopathy that cluster in families do not have a known genetic cause. iPSC-derived cardiomyocytes provide a mechanism to study the cardiomyocyte biology of cardiomyopathy patients noninvasively.

The goal of this project is to establish a biobank of extensively well-characterized iPSC lines for two highly prevalent familial forms of cardiovascular diseases: hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). For this purpose, in collaboration with the Wu Lab, the Snyder Lab collected peripheral blood from 103 HCM patients, 100 DCM patients, and 102 control donors. The isolated PBMCs were reprogrammed into iPSCs and serve as a shareable resource to the broader scientific community for cardiovascular and stem cell research.

Whole genome sequencing was completed for 100 HCM lines, 98 DCM lines, and 84 control lines. Meanwhile, one third of the iPSCs have been differentiated into cardiomyocytes, and the diseased transcriptome analyzed by RNA-seq, with this data set still growing. Additionally, iPSC-derived cardiomyocytes were treated with two cardiac drugs currently in clinical trial. RNA-seq after drug treatment is being used to understand patient differences in the severity of drug response. By combining the genomic, transcriptomic and clinical information together, the biobank will enable further analyses into the unique response of patient lines to the disease and drug treatments.

Publications

SETD7 Drives Cardiac Lineage Commitment through Stage-Specific Transcriptional Activation. Lee J et al. Cell Stem Cell. 2018 Mar 1;22(3):428-444.

Molecular and functional resemblance of differentiated cells derived from isogenic human iPSCs and SCNT-derived ESCs.Zhao MT et al. Proc Natl Acad Sci U S A. 2017 Dec 26;114(52):E11111-E11120.

Cell Type-Specific Chromatin Signatures Underline Regulatory DNA Elements in Human Induced Pluripotent Stem Cells and Somatic Cells. Zhao MT et al, Circ Res. 2017 Nov 10;121(11):1237-1250.

Genome-Wide Temporal Profiling of Transcriptome and Open Chromatin of Early Cardiomyocyte Differentiation Derived From hiPSCs and hESCs. Liu Q et al. Circ Res. 2017 Aug 4;121(4):376-391.

Primary files

Lab analysis

Biomarkers, protocols, clustering or other supplementary files supplied by the lab

Secondary analysis

Expression Matrix (lab-generated) | Expression matrix (UCSC) | QC Metrics

CESCG Center Standard Analysis

FastQC | Picard | RSEM | STAR | bigWig

Tertiary analysis

Cell Browser

Sample Psychic

SCIMITAR

RIGGLE

SurfacePlots

JCVI BioMarkers


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