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Series GSE118545 Query DataSets for GSE118545
Status Public on Oct 01, 2018
Title Single-nucleus transcriptomic survey of cell diversity and functional maturation in the postnatal mammalian hearts
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary A fundamental challenge in understanding cardiac biology and disease is that the remarkable heterogeneity in cell-type composition and functional states have not been well characterized at single-cell resolution in maturing and diseased mammalian hearts. Massively parallel single-nucleus RNA sequencing (snRNA-Seq) has emerged as a powerful tool to address these questions by interrogating the transcriptome of tens of thousands of nuclei isolated from fresh or frozen tissues. snRNA-Seq overcomes the technical challenge of isolating intact single cell from complex tissues including the maturing mammalian hearts, reduces biased recovery of easily dissociated cell types and minimizes aberrant gene expression during the whole-cell dissociation. Here we applied sNucDrop-Seq, a droplet microfluidics-based massively parallel snRNA-Seq method, to investigate the transcriptional landscape of postnatal maturing mouse hearts in both healthy or disease state. By profiling the transcriptome of nearly 20,000 nuclei, we identified major and rare cardiac cell types and revealed significant heterogeneity of cardiomyocytes, fibroblasts and endothelial cells in the postnatal developing heart. When applied to a mouse model of pediatric mitochondrial cardiomyopathy, we uncovered profound cell type-specific modifications of the cardiac transcriptional landscape at single-nucleus resolution, including changes of subtype composition, maturation states and functional remodeling of each cell type. Furthermore, we employed sNucDrop-Seq to decipher the cardiac cell type-specific gene regulatory network (GRN) of GDF15, a heart-derived hormone and clinically important diagnostic biomarker of heart disease. Together, our results present a rich resource for studying cardiac biology and provide new insights into heart disease using an approach broadly applicable to many fields of biomedicine.
Overall design Single-nucleus RNA sequencing analysis of postnatal maturing mouse hearts in both healthy or disease state
Contributor(s) Hu P, Liu J, Zhao J, Wilkins BJ, Lupino K, Wu H, Pei L
Citation(s) 30254108
Submission date Aug 14, 2018
Last update date Mar 25, 2019
Contact name Hao Wu
Phone 215-573-9360
Organization name University of Pennsylvania
Department Genetics
Lab Hao Wu
Street address 415 Curie Boulevard
City Philadelphia
State/province PA
ZIP/Postal code 19104
Country USA
Platforms (1)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (9)
GSM3332251 Ctrl-P6-1
GSM3332252 Ctrl-P6-2
GSM3332253 Ctrl-P6-3
BioProject PRJNA485989
SRA SRP157929

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Supplementary file Size Download File type/resource
GSE118545_RAW.tar 33.9 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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