Monthly Lab Seminar – September 14 2021 – 12:30 to 2:00 pm – Bordeaux Room (105 bd de l’Hôpital)
Michel Pucéat, Head of Physiopathology of Cardiac Development Team – Marseille Medical Genetics.
OCT4-Mediated Inflammation Induces Cell Reprogramming at the Origin of Cardiac Valve Development and Aortic Valve Calcification
Cell plasticity plays a key role in embryos by maintaining the differentiation potential of progenitors. Whether postnatal somatic cells reverse to an embryonic-like naïve state to regain plasticity, and re-differentiate into a cell type leading to a disease re-mains intriguing. Using genetic lineage tracing and single cell-RNA sequencing, we reveal that Oct4 is induced by Nfkb at E9.5 in a subset of mouse endocardial cells originating from the anterior heart forming field at the onset of EMT. These cells are primed to chondro-osteogenic cell fate. We observed OCT4 in adult valvular aortic cells leading to calcification of mouse and human valves and report that calcifying cells originate from the Oct4 embryonic lineage. Genetic deletion of Oct4 in the endocardial cell lineage prevents aortic stenosis and calcification of ApoE-/- mouse valve. We established a novel self-reprogramming Nfkb and Oct4-mediated inflammatory pathway triggering a dose-dependent cell reprogramming mechanism of valve calcification.