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Endocardial primary cilia and blood flow regulate EndoMT during endocardial cushion development [Single Nuc-RNAseq_IFT]

GSE252341 Mus musculus Expression profiling by high throughput sequencing 7 samples Submitted 2025/06/16 Platform GPL24247
Summary
Blood flow is critical for heart valve formation, and cellular mechanosensors are essential to translate flow into transcriptional regulation of development. Here, we identify a role for primary cilia in vivo in the spatial regulation of cushion formation, the first stage of valve development, by regionally controlling endothelial to mesenchymal transition (EndoMT) via modulation of Kruppel-like Factor 4 (Klf4). We find that high shear stress intracardiac regions decrease endocardial ciliation over cushion development, correlating with KLF4 downregulation and EndoMT progression. Mouse embryos constitutively lacking cilia exhibit a blood-flow dependent accumulation of KLF4 in these regions, independent of upstream left-right abnormalities, resulting in impaired cushion cellularization. snRNA-seq revealed that cilia KO endocardium fails to progress to late-EndoMT, retains endothelial markers and has reduced EndoMT/mesenchymal genes that KLF4 antagonizes. Together, these data identify a mechanosensory role for endocardial primary cilia in cushion development through regional regulation of KLF4.
Published in
Endocardial primary cilia and blood flow regulate EndoMT during endocardial cushion development
Berg K, Gorham J, Lundt F et al. · Nature cardiovascular research 2025 · PMID 40858839 · doi:10.1038/s44161-025-00697-z
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Also filed as BioProject PRJNA1060257 and SRA study SRP480959. Searching any of these in the dataset finder brings you back here.

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