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De Novo Generation of Somatic Stem Cells by YAP/TAZ
Published on: May 7, 2018
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A Retinoic Acid:YAP1 signaling axis controls atrial lineage commitment.
Elizabeth Abraham1, Brett Volmert2, Thomas Roule3
1Department of Cardiovascular Sciences, Aging + Cardiovascular Discovery Center, Temple University, Lewis Katz School of Medicine, Philadelphia, PA, USA.
Biorxiv : the Preprint Server for Biology
|July 19, 2024
Summary
Retinoic acid (RA) signaling guides heart development. This study identifies YAP1 as a key protein essential for RA to promote atrial cell fate and form the heart's upper chamber.
Area of Science:
- Developmental Biology
- Molecular Biology
- Cardiovascular Research
Background:
- Vitamin A/Retinoic Acid (RA) signaling is crucial for proper heart development.
- RA directs cardiac progenitor cells (CPCs) towards an atrial cardiomyocyte fate by regulating gene expression.
Purpose of the Study:
- To identify downstream effectors of RA signaling in CPCs.
- To elucidate the regulatory network governing atrial lineage specification.
Main Methods:
- Functional genomics: single-cell RNA sequencing (scRNA-seq) and single-nucleus ATAC sequencing (snATAC-seq) on human embryonic stem cell-derived CPCs.
- In vivo studies using conditional YAP1 knockout mouse embryos (Sox2-cre).
- Analysis in human embryonic stem cell-derived cardiac organoids.
Main Results:
- YAP1 and TEAD4 were identified as Hippo pathway effectors integrated into the atrial transcription factor network.
- YAP1 is essential for RA-enhancer activation in CPCs and atrial lineage gene expression (e.g., NR2F2) in vivo.
- YAP1 is required for atrial chamber formation but not ventricular formation in cardiac organoids.
Conclusions:
- YAP1 acts as a non-canonical effector of RA signaling.
- YAP1 is indispensable for the acquisition of atrial lineages during cardiogenesis.
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