ArticleNature cardiovascular research2025
Endocardial primary cilia and blood flow regulate EndoMT during endocardial cushion development.
Article in Nature cardiovascular research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- TAK1 operates at the primary cilium in non-canonical TGFB/BMP signaling to control heart development.PLoS biology · 2026Article
- Primary cilium disassembly - from mechanisms to roles in physiology and disease.Journal of cell science · 2026Review
- The primary cilium at the helm: gatekeeper of TGF-β superfamily signaling in development, homeostasis, and disease.Biochemical Society transactions · 2026Review
- A Continuum of Atrial Peristalsis Initiates the Bicuspid to Quadricuspid Valve Transition.bioRxiv : the preprint server for biology · 2026Article
- Targeting Endothelial PDK4-EndoMT Feedback Loop Mitigates the Development of Thoracic Aortic Dissection in Mice.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- Review
- Cardiac EndMT and EpiMT as a developmental continuum: integration of mechanical, metabolic, and epigenetic regulation.Frontiers in cell and developmental biology · 2026Review
- Elucidating Gene Functions in Congenital Heart Disease.Current treatment options in cardiovascular medicine · 2026Review
Corrections and comments
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5 authors.
Funding
Abstract
Valvular heart disease affects 2.5% of the population and is frequently associated with congenital heart disease. Blood flow is critical for valve formation, but the cellular mechanosensors translating flow into the transcriptional regulation of valve development remain undiscovered. Here, we identify that primary cilia and blood flow in mouse embryos regulate early valve development in vivo by regionally controlling endothelial-to-mesenchymal transition (EndoMT) through the modulation of Krüppel-like factor 4 (Klf4) in the endocardial cushions. Endocardial ciliation decreases during cushion development in regions of high shear stress, correlating with KLF4 downregulation and EndoMT progression. Mouse embryos lacking cilia exhibit blood flow-dependent accumulation of KLF4 and impaired cushion cellularization. Single-nucleus RNA sequencing revealed that the cilia-knockout and contractility-knockout endocardium fails to progress through EndoMT pseudostages, retains endothelial markers, and has reduced EndoMT and mesenchymal genes that KLF4 antagonizes. These data indicate that endocardial primary cilia function as mechanosensors in cushion development through the regional regulation of KLF4.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.