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| Status |
Public on Dec 30, 2021 |
| Title |
Endocardial/endothelial angiocrines regulate cardiomyocyte development and maturation and induce features of ventricular non-compaction |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Non-compaction cardiomyopathy is a devastating genetic disease caused by insufficient consolidation of ventricular wall muscle that can result in inadequate cardiac performance. Despite being the third most common cardiomyopathy, the mechanisms underlying the disease, including the cell types involved, are poorly understood. We have previously shown that endothelial cell-specific deletion of the chromatin remodeller gene Ino80 results in defective coronary vessel development that leads to ventricular non-compaction in embryonic mouse hearts. Here, we used single-cell RNA-sequencing to characterize endothelial and endocardial defects in Ino80-deficient hearts. We observed a pathological endocardial cell population in the non-compacted hearts and identified multiple dysregulated angiocrine factors that dramatically affected cardiomyocyte behaviour. We identified Col15A1 as a coronary vessel-secreted angiocrine factor, down-regulated by Ino80-deficiency, which functioned to promote cardiomyocyte proliferation. Furthermore, mutant endocardial and endothelial cells (ECs) AQ6 up-regulated expression of secreted factors, such as Tgfbi, Igfbp3, Isg15, and Adm, which decreased cardiomyocyte proliferation and increased maturation. These findings support a model where coronary ECs normally promote myocardial compaction through secreted factors, but that endocardial and ECs can secrete factors that contribute to non-compaction under pathological conditions.
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| Overall design |
Endothelial cell sigle cell RNA sequencing of mouse embryonic heart (Control) and Ino80 cKO at E15.5
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| Contributor(s) |
Rhee S, Paik DT, Nagelberg D, Tian L, Morrison AJ, Wu JC, Red-Horse K |
| Citation(s) |
34279605 |
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| Submission date |
May 27, 2021 |
| Last update date |
Dec 31, 2021 |
| Contact name |
Lei Tian |
| E-mail(s) |
tianlei@stanford.edu
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| Phone |
6502388262
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| Organization name |
Stanford's Postdoctoral Scholar programs
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| Street address |
1215 Welch Rd
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| City |
Stanford |
| State/province |
CA |
| ZIP/Postal code |
94305 |
| Country |
USA |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (2) |
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| Relations |
| BioProject |
PRJNA733034 |
| SRA |
SRP321544 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE175589_RAW.tar |
6.2 Mb |
(http)(custom) |
TAR (of H5) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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