Migratory and anti-fibrotic programmes define the regenerative potential of human cardiac progenitors.
Journal
Nature cell biology
ISSN: 1476-4679
Titre abrégé: Nat Cell Biol
Pays: England
ID NLM: 100890575
Informations de publication
Date de publication:
05 2022
05 2022
Historique:
received:
12
08
2021
accepted:
11
03
2022
pubmed:
14
5
2022
medline:
18
5
2022
entrez:
13
5
2022
Statut:
ppublish
Résumé
Heart regeneration is an unmet clinical need, hampered by limited renewal of adult cardiomyocytes and fibrotic scarring. Pluripotent stem cell-based strategies are emerging, but unravelling cellular dynamics of host-graft crosstalk remains elusive. Here, by combining lineage tracing and single-cell transcriptomics in injured non-human primate heart biomimics, we uncover the coordinated action modes of human progenitor-mediated muscle repair. Chemoattraction via CXCL12/CXCR4 directs cellular migration to injury sites. Activated fibroblast repulsion targets fibrosis by SLIT2/ROBO1 guidance in organizing cytoskeletal dynamics. Ultimately, differentiation and electromechanical integration lead to functional restoration of damaged heart muscle. In vivo transplantation into acutely and chronically injured porcine hearts illustrated CXCR4-dependent homing, de novo formation of heart muscle, scar-volume reduction and prevention of heart failure progression. Concurrent endothelial differentiation contributed to graft neovascularization. Our study demonstrates that inherent developmental programmes within cardiac progenitors are sequentially activated in disease, enabling the cells to sense and counteract acute and chronic injury.
Identifiants
pubmed: 35550611
doi: 10.1038/s41556-022-00899-8
pii: 10.1038/s41556-022-00899-8
pmc: PMC9106586
doi:
Substances chimiques
Nerve Tissue Proteins
0
Receptors, Immunologic
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
659-671Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2022. The Author(s).
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