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Adult type Maturation of Human Induced Pluripotent Stem Cells Derived Cardiomyocytes

ABSTRACT: Adult type Maturation of Human Induced Pluripotent Stem Cells Derived Cardiomyocytes

PROVIDER: PRJNA556635 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR9833050_1.fastq.gz	Fastqsanger.gz
	SRR9833050_2.fastq.gz	Fastqsanger.gz
	SRR9833060_1.fastq.gz	Fastqsanger.gz
	SRR9833060_2.fastq.gz	Fastqsanger.gz
	SRR9833070_1.fastq.gz	Fastqsanger.gz

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Adult type Maturation of Human Induced Pluripotent Stem Cells Derived Cardiomyocytes

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Project description:Rationale: Human pluripotent stem cells-derived cardiomyocytes (hPSC-CMs) exhibit the properties of fetal CMs, which limit their applications. Various methods have been used to promote maturation of hPSC-CMs; however, there is a lack of an unbiased and comprehensive method for accurate benchmarking of hPSC-CM maturation. Objective: We aim to develop an unbiased proteomics method integrating high-throughput top-down targeted proteomics and bottom-up global proteomics for accurate and comprehensive assessment of hPSC-CM maturation. Methods and Results: Utilizing hPSC-CMs from early- and late-stage two-dimensional monolayer culture and three-dimensional engineered cardiac tissue, we demonstrated high reproducibility and reliability of the top-down proteomics method, which enabled simultaneous quantification of contractile protein isoform expressions and their PTMs. This method allowed for the detection of known maturation-associated contractile protein alterations, and for the first time, identified contractile protein PTMs as promising new markers of maturation. By employing a global proteomics strategy, we identified candidate maturation markers important for sarcomere organization, cardiac excitability, and Ca2+ homeostasis; and validated these markers in the developing mouse cardiac ventricles. Conclusions: We established an unbiased proteomics method that can provide accurate and specific benchmarking of hPSC-CM maturation, and identified new markers of maturation. Furthermore, this integrated proteomics strategy laid a strong foundation for uncovering molecular basis underlying cardiac development and disease using hPSC-CMs.

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