The code here is for the interactive HeartExplorer portal that I developed. The web-portal refers to the dataset and the paper titled Defining the Fetal Gene Program at Single-Cell Resolution in Dilated Cardiomyopathy (DCM) and further details are as follows:
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A central dogma in cardiac biology is that the gene expression pattern observed in postnatal heart resemblance to those observed during fetal cardiac development in response to stress. The phenomenon of fetal gene re-activation in heart failure has been traditionally studied in cardiomyocytes, however, the extent to which the fetal gene program is recapitulated in other cardiac cell types is unknown. We present single-nucleus RNA sequencing (snRNAseq) of apical left ventricle tissue from fetal, early-onset DCM and their age-matched control (ND) samples to define the human fetal gene program in DCM, a common cause of heart failure in children and adults.
High-Throughput Sequencing, Dimensionality Reduction, Differential Gene Expression Analysis, Pseudobulk Analysis and Statistical Modeling
The single-cell transcriptomic data sets provided here permit the identification of cell type–specific gene dysregulation in DCM. In contrast with a previous single-cell transcriptional analysis of pediatric DCM, the current study included fetal and nondiseased control tissues, thus enabling precise cellular delineation of the fetal gene programs reactivated in DCM. Surprisingly, the phenomenon of fetal gene reactivation in DCM does not appear to be restricted to cardiomyocytes because a similar proportion of genes (<10%) adopts a fetal-like expression pattern in both cardiomyocytes and fibroblasts. This work provides a multicellular framework to identify the critical gene expression networks that underpin DCM disease pathogenesis in children. It will be important to determine whether these transcriptional mechanisms are also operative in other forms of heart failure including DCM in adults.
| Group | Age Range | Samples (n) | Nuclei Count |
|---|---|---|---|
| Fetal | 19–20 weeks | 3 | 27,136 |
| ND | 4–14 years | 3 | 16,445 |
| DCM | 5–10 years | 4 | 31,593 |
- All samples are derived from the left ventricle.
- Cell Type Identification
Annotate and cluster cell types within each group using unsupervised methods. - Cell Composition Analysis
Compare shifts in cell-type abundance across fetal, DCM, and their age-matched control samples. - Pathway and Transcriptional Analysis
Discover regulatory changes and transcription factor activity in DCM. - Fetal Gene Program Re-activation in DCM
Identify gene expression signatures indicative of fetal-like reprogramming in disease.
I have built an interactive web portal that permits interrogation of our dataset and, hence, increases the dataset’s accessibility and utility. To check our website, please visit www.HeartExplorer.org.
- Search by cell type or gene name
- View gene expression across conditions
- Perform pathway enrichment analysis across conditions
- Download selected data tables
All snRNAseq raw fastq.gz files including sample details have been deposited to Gene Expression Omnibus under accession No.:GSE185100. Besides the code available in this repository, comprehensive large-scale data analyses with its source code can also be retrieved from the Analysis Website and GitHub.
If you use this dataset or code, please cite:
@article{MehdiabadiCirculation2022,
author = {Neda Rahmani Mehdiabadi and et al.},
title = {Defining the Fetal Gene Program at Single-Cell Resolution in Dilated Cardiomyopathy},
journal = {Circulation},
year = {2022},
doi = {10.1161/CIRCULATIONAHA.121.057763},
url = {https://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.121.057763}
}This is a large single-nucleus RNAseq dataset from the Heart Regeneration group at Murdoch Children's Research Institute, Australia.