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Status |
Public on Apr 07, 2023 |
Title |
A Mesp1-dependent developmental breakpoint in transcriptional and epigenomic specification of early cardiac precursors |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing Genome binding/occupancy profiling by high throughput sequencing
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Summary |
Transcriptional networks governing cardiac precursor cell (CPC) specification are incompletely understood due in part to limitations in distinguishing CPCs from non-cardiac mesoderm in early gastrulation. We leveraged detection of early cardiac lineage transgenes within a granular single cell transcriptomic time course of mouse embryos to identify emerging CPCs and describe their transcriptional profiles. Mesp1, a transiently-expressed mesodermal transcription factor (TF), is canonically described as an early regulator of cardiac specification. However, we observed perdurance of CPC transgene-expressing cells in Mesp1 mutants, albeit mis-localized, prompting us to investigate the scope of Mesp1’s role in CPC emergence and differentiation. Mesp1 mutant CPCs failed to robustly activate markers of cardiomyocyte maturity and critical cardiac TFs, yet they exhibited transcriptional profiles resembling cardiac mesoderm progressing towards cardiomyocyte fates. Single cell chromatin accessibility analysis defined a Mesp1-dependent developmental breakpoint in cardiac lineage progression at a shift from mesendoderm transcriptional networks to those necessary for cardiac patterning and morphogenesis. These results reveal Mesp1-independent aspects of early CPC specification and underscore a Mesp1-dependent regulatory landscape required for progression through cardiogenesis.
This SuperSeries is composed of subseries.
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Overall design |
Study design referenced in individual series details.
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Citation(s) |
36994838 |
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Submission date |
Aug 05, 2022 |
Last update date |
Apr 09, 2023 |
Contact name |
Alexis Leigh Krup |
Organization name |
Gladstone Institutes
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Department |
Gladstone Institutes of Cardiovascular Disease
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Lab |
Bruneau Lab
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Street address |
1650 Owens Street
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City |
San Francisco |
State/province |
CA |
ZIP/Postal code |
94158 |
Country |
USA |
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Platforms (1) |
GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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Samples (24)
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This SuperSeries is composed of the following SubSeries: |
GSE208153 |
Transcriptional specification of early cardiac precursor cells at single cell resolution |
GSE210638 |
Chromatin accessibility profiles of early cardiac precursor cells at single cell resolution |
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Relations |
BioProject |
PRJNA866523 |