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| Status |
Public on Aug 17, 2020 |
| Title |
Single-Cell RNA-Seq and Patient-Specific iPSCs Reveal Endocardial Abnormalities in Hypoplastic Left Heart Syndrome |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Hypoplastic left heart syndrome (HLHS) is one of the most devastating forms of congenital heart defects. Previous studies have only focused on intrinsic defects in the myocardium. However, this does not sufficiently explain the abnormal development of the cardiac valve, septum, and vasculature, which are known to originate from the endocardium. Here, using single-cell RNA profiling, induced pluripotent stem cells, and fetal heart tissue with an underdeveloped left ventricle, we identified a developmentally impaired endocardial cell population in HLHS. The intrinsic endocardial deficits contributed to abnormal endothelial to mesenchymal transition, NOTCH signaling, and extracellular matrix organization, all of which are key factors in valve formation. Consequentially, endocardial abnormalities conferred reduced proliferation and maturation of cardiomyocytes through a disrupted fibronectin-integrin interaction. Several known HLHS de novo mutations all contributed to the abnormal endocardial gene expression through the alteration of promoter/enhancer activities. These mechanistic discoveries provide an alternative angle for early intervention and heart regeneration in HLHS.
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| Overall design |
This is the first study providing evidence that a developmentally impaired endocardium can contribute to the ventricular and valvular hypoplasia in hypoplastic left heart syndrome (HLHS), which may provide a novel therapeutic target for early intervention and heart regeneration for this condition.
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| Contributor(s) |
Miao Y, Tian L, Gu M |
| Citation(s) |
32810435 |
| Submission date |
Oct 16, 2019 |
| Last update date |
Jun 28, 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 (2) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (16)
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| GSM4125583 |
Control |
| GSM4125584 |
Hypoplastic left heart syndrome (HLHS) patient |
| GSM4125585 |
Normal fetal right ventricle vascular endothelial cadherin (CD144/CDH5) negative cells |
| GSM4125586 |
Normal fetal right ventricle vascular endothelial cadherin (CD144/CDH5) positive cells |
| GSM4125587 |
Normal fetal left ventricle vascular endothelial cadherin (CD144/CDH5) negative cells |
| GSM4125588 |
Normal fetal left ventricle vascular endothelial cadherin (CD144/CDH5) positive cells |
| GSM4125589 |
Undeveloped left heart fetal right ventricle vascular endothelial cadherin (CD144/CDH5) negative cells |
| GSM4125590 |
Undeveloped left heart fetal right ventricle vascular endothelial cadherin (CD144/CDH5) positive cells |
| GSM4125591 |
Undeveloped left heart fetal left ventricle vascular endothelial cadherin (CD144/CDH5) negative cells |
| GSM4125592 |
Undeveloped left heart fetal left ventricle vascular endothelial cadherin (CD144/CDH5) positive cells |
| GSM4125593 |
Normal iPSC-CMs co-cultured with normal iPSC-ECs 1 |
| GSM4125594 |
Normal iPSC-CMs co-cultured with normal iPSC-ECs 2 |
| GSM4125595 |
Normal iPSC-CMs co-cultured with normal iPSC-ECs 3 |
| GSM4125596 |
Normal iPSC-CMs co-cultured with Hypoplastic left heart syndrome (HLHS) iPSC-ECs 1 |
| GSM4125597 |
Normal iPSC-CMs co-cultured with Hypoplastic left heart syndrome (HLHS) iPSC-ECs 2 |
| GSM4125598 |
Normal iPSC-CMs co-cultured with Hypoplastic left heart syndrome (HLHS) iPSC-ECs 3 |
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| Relations |
| BioProject |
PRJNA577916 |
| SRA |
SRP225934 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE138979_RAW.tar |
141.8 Mb |
(http)(custom) |
TAR (of H5) |
| GSE138979_gene.count.txt.gz |
4.7 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
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