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RNA-Seq of isogenic human iPS cell-derived cardiomyocytes with RBM20 mutations created by genome editing

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE175886 | GEO | 2021/06/01

REPOSITORIES: GEO

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RNA-Seq of isogenic human iPS cell-derived cardiomyocytes with RBM20 mutations created by genome editing (eCLIP)

Project description:Homozygous R636S mutation was created by genome editing in an iPS cell line generated from a healthy female patient. Mutant and wild-type cells were differentiated into cardiomyocytes by modulating the WNT signaling pathway, and then are subjected to the lactate purification method. eCLIP was performed to identify targets of RBM20 in mutant and wild-type iPSC-CMs.

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RNA-Seq of isogenic human iPS cell-derived cardiomyocytes with RBM20 mutations created by genome editing [RNA-Seq]

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RNA-Seq of isogenic human iPS cell-derived cardiomyocytes with RBM20 mutations created by genome editing (WTB RNA-Seq)

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RNA-Seq of isogenic human iPS cell-derived cardiomyocytes with RBM20 mutations created by genome editing (RiboMinus RNA-Seq)

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RNA-Seq of isogenic human iPS cell-derived cardiomyocytes with RBM20 mutations created by genome editing

Project description:RNA-Seq of isogenic human iPS cell-derived cardiomyocytes with RBM20 mutations created by genome editing

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RNA-Seq of isogenic human iPS cell-derived cardiomyocytes with RBM20 mutations created by genome editing (eCLIP)

Project description:RNA-Seq of isogenic human iPS cell-derived cardiomyocytes with RBM20 mutations created by genome editing (eCLIP)

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RNA-Seq of isogenic human iPS cell-derived cardiomyocytes with RBM20 mutations created by genome editing [RNA-Seq]

Project description:RNA-Seq of isogenic human iPS cell-derived cardiomyocytes with RBM20 mutations created by genome editing [RNA-Seq]

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RNA-Seq of isogenic human iPS cell-derived cardiomyocytes with RBM20 mutations created by genome editing (WTB RNA-Seq)

Project description:RNA-Seq of isogenic human iPS cell-derived cardiomyocytes with RBM20 mutations created by genome editing (WTB RNA-Seq)

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Project description:RNA-Seq of isogenic human iPS cell-derived cardiomyocytes with RBM20 mutations created by genome editing (RiboMinus RNA-Seq)

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Genome-wide CRISPR/Cas9 screening in human iPS derived cardiomyocytes uncovers novel mediators of doxorubicin cardiotoxicity.

Project description:Human induced pluripotent stem (iPS) cell technologies coupled with genetic engineering now facilitate the study of the molecular underpinnings of disease in relevant human cell types. Application of CRISPR/Cas9-based approaches for genome-scale functional screening in iPS-derived cells, however, has been limited by technical constraints, including inefficient transduction in pooled format, loss of library representation, and poor cellular differentiation. Herein, we present optimized approaches for whole-genome CRISPR/Cas9 based screening in human iPS derived cardiomyocytes with near genome-wide representation at both the iPS and differentiated cell stages. As proof-of-concept, we perform a screen to investigate mechanisms underlying doxorubicin mediated cell death in iPS derived cardiomyocytes. We identified two poorly characterized, human-specific transporters (SLCO1A2, SLCO1B3) whose loss of function protects against doxorubicin-cardiotoxicity, but does not affect cell death in cancer cells. This study provides a technical framework for genome-wide functional screening in iPS derived cells and identifies new targets to mitigate doxorubicin-cardiotoxicity in humans.

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