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| Status |
Public on Jul 30, 2018 |
| Title |
Cardiomyocyte gene programs encoding morphological and functional signatures in cardiac hypertrophy and failure (RNA-Seq) |
| Organisms |
Homo sapiens; Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Pressure overload induces a transition from cardiac hypertrophy to heart failure, but its underlying mechanisms remain elusive. Here we reconstruct a trajectory of cardiomyocyte remodeling and clarify distinct cardiomyocyte gene programs encoding morphological and functional signatures in cardiac hypertrophy and failure, by integrating single-cardiomyocyte transcriptome with cell morphology, epigenomic state and heart function. During early hypertrophy, cardiomyocytes activate mitochondrial translation/metabolism genes, whose expression is correlated with cell size and linked to ERK1/2 and NRF1/2 transcriptional networks. Persistent overload leads to a bifurcation into adaptive and failing cardiomyocytes, and p53 signaling is specifically activated in late hypertrophy. Cardiomyocyte-specific p53 deletion shows that cardiomyocyte remodeling is initiated by p53-independent mitochondrial activation and morphological hypertrophy, followed by p53-dependent mitochondrial inhibition, morphological elongation, and heart failure gene program activation. Human single-cardiomyocyte analysis validates the conservation of the pathogenic transcriptional signatures. Collectively, cardiomyocyte identity is encoded in transcriptional programs that orchestrate morphological and functional phenotypes.
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| Overall design |
Integrative analysis of single-cardiomyocyte RNA-seq of pressure-overload-induced heart failure model mice and heart failure patients with dilated cardiomyopathy, single-cell morphology, cardiac function and genetic perturbation
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| Contributor(s) |
Nomura S, Satoh M, Fujita T, Higo T, Sumida T, Ko T, Yamaguchi T, Aburatani H, Komuro I |
| Citation(s) |
30375404, 32868781, 33854108, 35672400 |
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| Submission date |
Feb 21, 2017 |
| Last update date |
Jun 16, 2022 |
| Contact name |
Seitaro Nomura |
| E-mail(s) |
senomura-cib@umin.ac.jp
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| Phone |
81338155411
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| Organization name |
The University of Tokyo
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| Department |
Department of Cardiovascular Medicine
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| Street address |
7-3-1, Hongo, Bunkyo-ku
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| City |
Tokyo |
| State/province |
Select a State or Province |
| ZIP/Postal code |
113-8655 |
| Country |
Japan |
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| Platforms (2) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (1190)
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| This SubSeries is part of SuperSeries: |
| GSE95143 |
Cardiomyocyte stress-response gene modules regulate cardiac hypertrophy and failure |
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| Relations |
| BioProject |
PRJNA376181 |
| SRA |
SRP100463 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE95140_Integrative_data_of_single-cell_RNA-seq_and_morphology.txt.gz |
1.0 Mb |
(ftp)(http) |
TXT |
| GSE95140_human_single-cardiomyocyte_RNA-seq.txt.gz |
12.2 Mb |
(ftp)(http) |
TXT |
| GSE95140_single-cardiomyocyte_RNA-seq.txt.gz |
18.5 Mb |
(ftp)(http) |
TXT |
| GSE95140_single-cardiomyocyte_RNA-seq_of_p53CKO_mice.txt.gz |
2.1 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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