| First Author | Farrar EJ | Year | 2021 |
| Journal | Sci Adv | Volume | 7 |
| Issue | 45 | Pages | eabf7910 |
| PubMed ID | 34739324 | Mgi Jnum | J:316207 |
| Mgi Id | MGI:6832748 | Doi | 10.1126/sciadv.abf7910 |
| Citation | Farrar EJ, et al. (2021) OCT4-mediated inflammation induces cell reprogramming at the origin of cardiac valve development and calcification. Sci Adv 7(45):eabf7910 |
| abstractText | 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 Pou5f1 (Pit-Oct-Unc, OCT4) in the endocardial cell lineage prevents aortic stenosis and calcification of ApoEâ/â mouse valve. We established previously unidentified self-cell reprogramming NFκB- and OCT4-mediated inflammatory pathway triggering a dose-dependent mechanism of valve calcification. |
