Find Paper, Faster
Example:10.1021/acsami.1c06204 or Chem. Rev., 2007, 107, 2411-2502
Epicardium-derived cells organize through tight junctions to replenish cardiac muscle in salamanders
Nature Cell Biology  (IF28.213),  Pub Date : 2022-05-12, DOI: 10.1038/s41556-022-00902-2
Elif Eroglu, Christopher Y. T. Yen, Yat-Long Tsoi, Nevin Witman, Ahmed Elewa, Alberto Joven Araus, Heng Wang, Tamara Szattler, Chimezie H. Umeano, Jesper Sohlmér, Alexander Goedel, András Simon, Kenneth R. Chien

The contribution of the epicardium, the outermost layer of the heart, to cardiac regeneration has remained controversial due to a lack of suitable analytical tools. By combining genetic marker-independent lineage-tracing strategies with transcriptional profiling and loss-of-function methods, we report here that the epicardium of the highly regenerative salamander species Pleurodeles waltl has an intrinsic capacity to differentiate into cardiomyocytes. Following cryoinjury, CLDN6+ epicardium-derived cells appear at the lesion site, organize into honeycomb-like structures connected via focal tight junctions and undergo transcriptional reprogramming that results in concomitant differentiation into de novo cardiomyocytes. Ablation of CLDN6+ differentiation intermediates as well as disruption of their tight junctions impairs cardiac regeneration. Salamanders constitute the evolutionarily closest species to mammals with an extensive ability to regenerate heart muscle and our results highlight the epicardium and tight junctions as key targets in efforts to promote cardiac regeneration.