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Article Dans Une Revue Science Advances Année : 2021

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

Résumé

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 ApoE−/− mouse valve. We established previously unidentified self-cell reprogramming NFκB- and OCT4-mediated inflammatory pathway triggering a dose-dependent mechanism of valve calcification.
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Origine : Publication financée par une institution
Licence : CC BY NC - Paternité - Pas d'utilisation commerciale

Dates et versions

hal-03662357 , version 1 (26-01-2023)

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Paternité - Pas d'utilisation commerciale

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Emily Farrar, Emilye Hiriart, Ablajan Mahmut, Bernd Jagla, David Peal, et al.. OCT4-mediated inflammation induces cell reprogramming at the origin of cardiac valve development and calcification. Science Advances , 2021, 7 (45), pp.eabf7910. ⟨10.1126/sciadv.abf7910⟩. ⟨hal-03662357⟩
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