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Effects of Spaceflight on Human Induced Pluripotent Stem Cell-Derived Cardiomyocyte Structure and Function

ABSTRACT: Effects of Spaceflight on Human Induced Pluripotent Stem Cell-Derived Cardiomyocyte Structure and Function

PROVIDER: PRJNA564518 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR10084977_1.fastq.gz	Fastqsanger.gz
	SRR10084977_2.fastq.gz	Fastqsanger.gz
	SRR10084978_1.fastq.gz	Fastqsanger.gz
	SRR10084978_2.fastq.gz	Fastqsanger.gz
	SRR10084979_1.fastq.gz	Fastqsanger.gz

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Effects of Spaceflight on Human Induced Pluripotent Stem Cell-Derived Cardiomyocyte Structure and Function

Project description:With extended stays aboard the International Space Station (ISS) becoming commonplace, there is a need to better understand the effects of microgravity on cardiac function. We utilized human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) to study the effects of microgravity on cell-level cardiac function and gene expression. The hiPSC-CMs were cultured aboard the ISS for 5.5 weeks and their gene expression, structure, and functions were compared to ground control hiPSC-CMs. Exposure to microgravity on the ISS caused alterations in hiPSC-CM calcium handling. RNA-sequencing analysis demonstrated 2,635 genes were differentially expressed among flight, post-flight, and ground control samples, including genes involved in mitochondrial metabolism. This study represents the first use of hiPSCs to model the effects of spaceflight on human cardiomyocyte structure and function.

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Project description:With extended stays aboard the International Space Station (ISS) becoming commonplace, there is a need to better understand the effects of microgravity on cardiac function. We utilized human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) to study the effects of microgravity on cell-level cardiac function and gene expression. The hiPSC-CMs were cultured aboard the ISS for 5.5 weeks and their gene expression, structure, and functions were compared with ground control hiPSC-CMs. Exposure to microgravity on the ISS caused alterations in hiPSC-CM calcium handling. RNA-sequencing analysis demonstrated that 2,635 genes were differentially expressed among flight, post-flight, and ground control samples, including genes involved in mitochondrial metabolism. This study represents the first use of hiPSC technology to model the effects of spaceflight on human cardiomyocyte structure and function.

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Spaceflight alters protein levels and gene expression associated with cell survival and metabolic characteristics in human cardiac spheroids

Project description:Cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) possess tremendous advantage for cardiac regeneration. However, cell survival is challenging upon cell transplantation. Since microgravity can profoundly affect cellular properties, we investigated the effect of spaceflight on hiPSC-CMs. Cardiac spheroids derived from hiPSCs were transported to the International Space Station (ISS) via the SpaceX Crew-8 mission and cultured under space microgravity for 8 days. Beating cardiac spheroids were observed on the ISS and upon successful experimentation by the astronauts in space, the live cultures were returned to Earth. These cells had normal displacement (an indicator of contraction) and Ca2+ transient parameters in 3D live cell imaging. Proteomics analysis revealed that spaceflight upregulated many proteins involved in metabolism (n=90), cellular component of mitochondrion (n=62) and regulation of proliferation (n=10). Specific metabolic pathways upregulated by spaceflight included glutathione metabolism, biosynthesis of amino acids, and pyruvate metabolism. In addition, spaceflight upregulated cellular stress response- and survival-related proteins and the AMPK signaling pathway, a master regulator of metabolism. Transcriptomic profiles indicated that spaceflight upregulated genes associated with cardiomyocyte development, and cellular components of cardiac structure and mitochondrion. Furthermore, spaceflight upregulated genes in metabolic pathways associated with cell survival such as glycerophospholipid metabolism and glycerolipid metabolism. These findings indicate that short-term exposure of the space environment to 3D hiPSC-CMs led to significant changes in protein levels and gene expression involved in cell survival and metabolism.

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