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Ultra-Efficient Exosome-Guided Direct Reprogramming of Fibroblasts into Functional Cardiomyocytes [miRNA-Seq]

ABSTRACT: Ultra-Efficient Exosome-Guided Direct Reprogramming of Fibroblasts into Functional Cardiomyocytes [miRNA-Seq]

PROVIDER: PRJNA699853 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13639969.fastq.gz	Fastqsanger.gz
	SRR13639970.fastq.gz	Fastqsanger.gz
	SRR13639971.fastq.gz	Fastqsanger.gz
	SRR13639972.fastq.gz	Fastqsanger.gz

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Ultra-Efficient Exosome-Guided Direct Reprogramming of Fibroblasts into Functional Cardiomyocytes

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Ultra-Efficient Exosome-Guided Direct Reprogramming of Fibroblasts into Functional Cardiomyocytes [Quant-seq]

Project description:Ultra-Efficient Exosome-Guided Direct Reprogramming of Fibroblasts into Functional Cardiomyocytes [Quant-seq]

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Ultra-Efficient Exosome-Guided Direct Reprogramming of Fibroblasts into Functional Cardiomyocytes [miRNA-Seq]

Project description:Direct lineage conversion holds great promise in the regenerative medicine field for restoring damaged tissues using functionally engineered counterparts. However, current methods of direct lineage conversion, even those employing virus-mediated transgenic expression of tumorigenic factors, are extremely inefficient (~25%). Thus, advanced methodologies capable of revolutionizing efficiency and addressing safety issues are key to clinical translation of these technologies. Here, we propose an exosome-guided, non-viral, direct-lineage conversion strategy to enhance transdifferentiation of fibroblasts to induced cardiomyocyte-like cells (iCMs). Exosomes produced during the cardiac differentiation process of embryonic stem cells (ESCs) are able to achieve extremely high reprogramming efficiency (>60%) by generating functional iCMs from mouse embryonic fibroblasts via a cardiac precursor-like stage rather than a pluripotent state. The resulting iCMs possess typical cardiac Ca2+ transients and electrophysiological features, and exhibit global gene expression profiles similar to those of cardiomyocytes. The optimized reprogramming conditions produce beating iCM clusters ~3-fold more efficiently than conventional methods. This is the first demonstration of the use of exosomes derived from ESCs undergoing cardiac differentiation as biomimetic tools to induce direct cardiac reprogramming with greatly improved efficiency, establishing a general, more readily accessible platform for broadly generating a variety of specialized somatic cells through direct lineage conversion.

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Ultra-Efficient Exosome-Guided Direct Reprogramming of Fibroblasts into Functional Cardiomyocytes [Quant-seq]

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Ultra-Efficient Exosome-Guided Direct Reprogramming of Fibroblasts into Functional Cardiomyocytes

Project description:This SuperSeries is composed of the SubSeries listed below.

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Laminin-guided highly efficient endothelial commitment from human pluripotent stem cells

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Am80 activates cardiomyocytes cell cycle via retinoic acid receptor for efficient transplantation

Project description:Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-cardiomyocytes) are promising sources for the regenerative therapy to treat heart failure. To realize this therapy, the engraftment potential of hiPSC-cardiomyocytes following the injection into the host heart should be improved. Here, we established the efficient method to analyze the cell cycle activity of hiPSC-cardiomyocytes using Fluorescence Ubiquitination-based Cell Cycle Indicator (FUCCI) system. High-throughput screening analysis using FUCCI-expressing hiPSC-cardiomyocytes identified a retinoic acid receptor (RAR) agonist, Am80, as an effective cell cycle activator in hiPSC-cardiomyocytes. The transplantation of hiPSC-cardiomyocytes treated by Am80 prior to the injection significantly enhanced the engraftment into the damaged mouse heart for 6 months. RNA sequencing analysis in Am80-treated iPSC-cardiomyocytes revealed that both RARA and RARB played important roles in the Am80-mediated cell cycle activation in hiPSC-cardiomyocytes. Collectively, this study highlights the effectiveness of FUCCI system to easily analyze the cell cycle status in hiPSC-cardiomyocytes and the cell cycle activation by Am80 is the possible strategy to increase the graft size following the cell transplantation into the damaged heart.

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