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Epicardium-derived cells organize through tight junctions to replenish cardiac muscle in salamanders

Eroglu, Elif ; Yen, Christopher Y.T. ; Tsoi, Yat Long ; Witman, Nevin ; Elewa, Ahmed ; Joven Araus, Alberto ; Wang, Heng ; Szattler, Tamara ; Umeano, Chimezie H. LU and Sohlmér, Jesper , et al. (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.

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organization
publishing date
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
2024-08-08 12:51:30
@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}},
}