Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

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

ABSTRACT: 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 enriched by spaceflight included glutathione metabolism, biosynthesis of amino acids, and pyruvate metabolism. In addition, spaceflight upregulated proteins in cellular stress response, cell survival, and the AMPK signaling pathway, a master regulator of metabolism.

INSTRUMENT(S): Orbitrap Exploris 480

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Chunhui Xu

PROVIDER: MSV000096580 | MassIVE | Tue Dec 03 08:58:00 GMT 2024

REPOSITORIES: MassIVE

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

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.

2025-01-10 | GSE277713 | GEO

Microgravity on the International Space Station promotes survival and proliferation of human stem cell cardiomyocytes

Project description:Efficient generation of functional cardiomyocytes from human induced pluripotent stem cells (hiPSC-CMs) is critical for their use in regenerative medicine and other applications. In this study, we evaluated the effect of space microgravity (µg) on the differentiation of hiPSC-derived cardiac progenitors compared with parallel 1g condition on the International Space Station. Cryopreserved 3D cardiac progenitors derived from hiPSCs were cultured for 3 weeks. Compared with 1g culture, the µg culture had larger sphere sizes, increased expression of proliferation markers, higher counts of nuclei, and higher cell viability. Highly enriched cardiomyocytes generated in µg had appropriate gene expression and cardiac structure as well as improved function including contractility and Ca2+ handling. RNA-seq analysis of 3-day cultures revealed that short-term exposure of cardiac progenitor spheres to space microgravity upregulated genes involved in cell proliferation, cardiac differentiation, and contraction. These results indicate that space microgravity increased survival and proliferation of hiPSC-CMs and improved their structures and functions.

2022-09-08 | GSE188793 | GEO

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.

2019-11-07 | GSE137081 | GEO

Space microgravity increases expression of genes associated with proliferation and differentiation in human cardiac spheres

Project description:Previously, we reported upregulation of cardiac proliferation in cardiac progenitors derived from human induced pluripotent stem cells (hiPSC-CPCs) that were exposed to space microgravity for 3 days. The overall objective of this investigation was to understand how long-term exposure to microgravity affects the expansion and differentiation of hiPSC-CPCs. Cryopreserved cardiomyocytes derived from human-induced pluripotent stem cells (hiPSC-CMs) were exposed to space microgravity for 3 weeks in the International Space Station (ISS) and retrieved for transcriptomic profiling. RNA-seq analysis and gene ontology analysis revealed upregulation of cardiac tissue function and morphological terms while downregulating inflammation and ECM regulation terms. Upregulation of genes associated with cell cycle regulation and proliferation were notable as well. Combined with previous work, these results suggest that space microgravity improved cardiac differentiation and structure formation and potentially, proliferation.

2023-12-04 | GSE228063 | GEO

Total protein profiles of human induced pluripotent stem cell-derived cardiomyocytes in response to four tyrosine kinase inhibitors

Project description:Drug-induced cardiotoxicity is a widespread clinical issue affecting numerous drug classes and remains difficult to treat. One such drug class is Tyrosine Kinase Inhibitors (TKIs), which cause varying degrees of contraction-related cardiotoxicity usually after weeks of exposure. Understanding molecular mechanisms underlying both acute and chronic toxicity of TKIs could help identify new treatment opportunities. Here, we presented transcriptome responses to four TKIs (Sunitinib, Sorafenib, Lapatinib and Erlotinib) across 3 doses and 4 time points in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Gene expression evolved continually under drug treatment and revealed changes in several biological networks that were associated with cardiac metabolism and contraction. These changes were confirmed by proteomics and resulted in metabolic and structural remodeling of hiPSC-CMs. One of the metabolic remodeling was the increased aerobic glycolysis induced by Sorafenib, which is an adaptive response in preserving cell survival under Sorafenib treatment. Drug adaptation in cardiac cells may represent new targets for managing chronic forms of TKI-induced cardiotoxicity.

2019-05-16 | PXD012043 | Pride

Human-iPSC-Derived Cardiac Stromal Cells Enhance Maturation in 3D Cardiac Microtissues and Reveal Non-cardiomyocyte Contributions to Heart Disease

Project description:Cardiomyocytes (CMs) from human induced pluripotent stem cells (hiPSCs) are functionally immature, but this is improved by incorporation into engineered tissues or forced contraction. Here, we showed that tri-cellular combinations of hiPSC-derived CMs, cardiac fibroblasts (CFs), and cardiac endothelial cells also enhance maturation in easily constructed, scaffold-free, three-dimensional microtissues (MTs). hiPSC-CMs in MTs with CFs showed improved sarcomeric structures with T-tubules, enhanced contractility, and mitochondrial respiration and were electrophysiologically more mature than MTs without CFs. Interactions mediating maturation included coupling between hiPSC-CMs and CFs through connexin 43 (CX43) gap junctions and increased intracellular cyclic AMP (cAMP). Scaled production of thousands of hiPSC-MTs was highly reproducible across lines and differentiated cell batches. MTs containing healthy-control hiPSC-CMs but hiPSC-CFs from patients with arrhythmogenic cardiomyopathy strikingly recapitulated features of the disease. Our MT model is thus a simple and versatile platform for modeling multicellular cardiac diseases that will facilitate industry and academic engagement in high-throughput molecular screening.

2020-05-26 | GSE147694 | GEO

Human-iPSC-Derived Cardiac Stromal Cells Enhance Maturation in 3D Cardiac Microtissues and Reveal Non-cardiomyocyte Contributions to Heart Disease

2020-05-26 | GSE116464 | GEO

Proteomic analysis of mitochondrial biogenesis in cardiomyocytes differentiated from human induced pluripotent stem cell

Project description:Mitochondria play a crucial role in the differentiation and maturation of human cardiomyocytes (CMs). To identify mitochondrial pathways and regulators that are involved in cardiac differentiation and maturation, we examined human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Proteomic analysis was performed on enriched mitochondrial protein extracts isolated from hiPSC-CMs differentiated from dermal fibroblasts (dFCM) and cardiac fibroblasts (cFCM), at different days of differentiation (between 12 and 115 days), and also from adult and neonatal mouse hearts for comparison. Mitochondrial proteins with a ≥2-fold change between differentiation time points in dFCMs and cFCMs, and between adult versus neonatal mouse hearts, were subjected to Ingenuity Pathway Analysis (IPA), and some upregulated proteins were validated by immunoblotting. The highest significant upregulation was in metabolic pathways for fatty acid oxidation (FAO), the tricarboxylic acid (TCA) cycle, oxidative phosphorylation (OXPHOS) and branched chain amino acid (BCAA) catabolism. The top upstream regulators predicted by IPA were- peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1-a), the insulin receptor and the retinoblastoma protein (Rb) transcriptional repressor. In addition, IPA and immunoblotting showed substantial upregulation of the mitochondrial LonP1 protease, which regulates mitochondrial proteostasis, energetics and metabolism. Using this proteomics approach, we have identified key metabolic and intracellular signaling pathways that are up- and down- regulated during the biogenesis of mitochondria in differentiating and maturing cardiac myocytes.

2022-05-19 | PXD014317 | Pride

Dual inhibition of MAPK and PI3K/AKT pathways enhances maturation of human iPSC-derived cardiomyocytes

Project description:Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) provide great opportunities for mechanistic dissection of human cardiac pathophysiology; however, hiPSC-CMs remain immature relative to the adult heart. To identify novel signaling pathways driving the maturation process during heart development, we analyzed published transcriptional and epigenetic datasets from hiPSC-CMs, prenatal and postnatal human hearts. These analyses revealed that several components of the MAPK and PI3K-AKT pathways are downregulated in the postnatal heart. Here, we show that dual inhibition of these pathways for only 5 days significantly enhances the maturation of day-30 hiPSC-CMs in many domains: hypertrophy, multinucleation, metabolism, t-tubule density, calcium handling, and electrophysiology, many equivalent to day-60 hiPSC-CMs. These data indicate that the MAPK/PI3K/AKT pathways are involved in cardiomyocyte maturation and provide proof-of-concept for the manipulation of key signaling pathways for optimal hiPSC-CM maturation, a critical aspect of faithful in vitro modeling of cardiac pathologies and subsequent drug discovery.

2022-08-04 | GSE187308 | GEO

Maturation of hiPSC-derived cardiomyocytes in tri-cellular cardiac microtissues promotes adult alternative splicing of SCN5A revealing effects of mutations in cardiac disease

Project description:Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are used to examine in vitro the effect of mutations in the cardiac sodium channel gene SCN5A, associated with cardiac arrhythmias. Postnatally SCN5A undergoes a fetal-to-adult isoform switch, but hiPSC-CMs in conventional 2-dimensional cultures are fetal-like. This impedes evaluation of mutations in the adult isoform. Here, we derived hiPSC-CMs from a patient carrying compound mutations in the adult SCN5A exon 6B and in exon 4 and generated isogenic corrected lines. In hiPSC-CM 2-dimensional culture, exon 6B mutation did not affect single-cell electrophysiology because of its limited expression. CRISPR/Cas9-mediated excision of the fetal exon 6A with did not promote adult SCN5A expression, rather it impaired the splicing. By maturing hiPSC-CMs in three-dimensional tri-cell type cardiac microtissues, SCN5A underwent isoform switch and revealed the functional effect of exon 6B mutation. Upregulation of the splicing factor MBNL1 in hiPSC-CMs either by culture in microtissues or by overexpression was sufficient to promote exon 6B inclusion. Our results support the ability to study developmentally regulated cardiac genes and postnatal cardiac arrhythmias using hiPSC cardiac cells.

2023-05-03 | GSE180290 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data