OCT4-mediated inflammation induces cell reprogramming at the origin of cardiac valve development and calcification

Cell plasticity plays a key role in embryos by maintaining the differentiation potential of progenitors. Whether postnatal somatic cells revert to an embryonic-like naive 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 kappa B (NF kappa B) 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 Pou5f1 (Pit-Oct-Unc, OCT4) in the endocardial cell lineage prevents aortic stenosis and calcification of ApoE(-/-) mouse valve. We established previously unidentified self-cell reprogramming NF kappa B- and OCT4-mediated inflammatory pathway triggering a dose-dependent mechanism of valve calcification.

Automated summary

Studies have found that a subset of mouse endocardial cells express Oct4 induced by nuclear factor kappa B (NF kappa B) during the process of transition starting at day 9.5 of embryo development. These cells acquire a chondro-osteogenic fate and in adulthood lead to valve calcification. Genetic deletion of OCT4 can prevent aortic stenosis and valve calcification.