OCT4-mediated inflammation induces cell reprogramming at the origin of cardiac valve development and calcification.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 34739324.
- Also identified by DOI 10.1126/sciadv.abf7910 and PMC identifier 8570594.
- Licence recorded as CC BY-NC.
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Abstract
Cell plasticity plays a key role in embryos by maintaining the differentiation potential of progenitors. Whether postnatal somatic cells revert to an embryonic-like naïve state regaining plasticity and redifferentiate into a cell type leading to a disease remains intriguing. Using genetic lineage tracing and single-cell RNA sequencing, we reveal that Oct4 is induced by nuclear factor κB (NFκB) at embyronic day 9.5 in a subset of mouse endocardial cells originating from the anterior heart forming field at the onset of endocardial-to-mesenchymal transition. These cells acquired a chondro-osteogenic fate. OCT4 in adult valvular aortic cells leads to calcification of mouse and human valves. These calcifying cells originate from the Oct4 embryonic lineage. Genetic deletion of <i>Pou5f1 (Pit-Oct-Unc</i>, OCT4) in the endocardial cell lineage prevents aortic stenosis and calcification of <i>ApoE</i><sup>−/−</sup> mouse valve. We established previously unidentified self-cell reprogramming NFκB- and OCT4-mediated inflammatory pathway triggering a dose-dependent mechanism of valve calcification.