Epicardium-derived cells organize through tight junctions to replenish cardiac muscle in salamanders
(2022) In Nature Cell Biology 24(5). p.645-658- Abstract
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.... (More)
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.
(Less)
- author
- organization
- publishing date
- 2022-05
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Nature Cell Biology
- volume
- 24
- issue
- 5
- pages
- 14 pages
- publisher
- Nature Publishing Group
- external identifiers
-
- scopus:85129789828
- pmid:35550612
- ISSN
- 1465-7392
- DOI
- 10.1038/s41556-022-00902-2
- language
- English
- LU publication?
- yes
- additional info
- Publisher Copyright: © 2022, The Author(s).
- id
- 14e8d4b6-48b9-4db6-ad08-051251ee530b
- date added to LUP
- 2022-08-26 15:04:51
- date last changed
- 2024-09-19 17:13:04
@article{14e8d4b6-48b9-4db6-ad08-051251ee530b, abstract = {{<p>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<sup>+</sup> 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<sup>+</sup> 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.</p>}}, author = {{Eroglu, Elif and Yen, Christopher Y.T. and Tsoi, Yat Long and Witman, Nevin and Elewa, Ahmed and Joven Araus, Alberto and Wang, Heng and Szattler, Tamara and Umeano, Chimezie H. and Sohlmér, Jesper and Goedel, Alexander and Simon, András and Chien, Kenneth R.}}, issn = {{1465-7392}}, language = {{eng}}, number = {{5}}, pages = {{645--658}}, publisher = {{Nature Publishing Group}}, series = {{Nature Cell Biology}}, title = {{Epicardium-derived cells organize through tight junctions to replenish cardiac muscle in salamanders}}, url = {{http://dx.doi.org/10.1038/s41556-022-00902-2}}, doi = {{10.1038/s41556-022-00902-2}}, volume = {{24}}, year = {{2022}}, }