Absence of a prolonged macrophage and B cell response inhibits heart regeneration in the Mexican cavefish.
7 affiliations
- 1Institute of Developmental and Regenerative Medicine, Old Road Campus, University of Oxford, Oxford, UK.
- 2Department of Physiology, Anatomy & Genetics, University of Oxford, Oxford, UK.
- 3School of Biochemistry and Biomedical Sciences, University of Bristol, Bristol, UK.
- 4King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia.
- 5Bioinfo, Plantagenet, ON, Canada.
- 6Institute of Developmental and Regenerative Medicine, Old Road Campus, University of Oxford, Oxford, UK. [email protected].
- 7Department of Physiology, Anatomy & Genetics, University of Oxford, Oxford, UK. [email protected].
Abstract
A balanced immune response after cardiac injury is crucial to successful heart regeneration, but knowledge of what distinguishes a regenerative from a scarring response is still limited. The Mexican cavefish Astyanax mexicanus provides a unique comparative model to study heart regeneration and scarring within a single species. Astyanax surface-dwelling fish are capable of heart regeneration, whereas, like the human heart, their cave-dwelling Pachón counterparts form a permanent scar. Using single-cell transcriptomics and immune perturbations, we identify two distinct and largely sequential immune mechanisms driving regeneration in surface fish. First, late-present macrophages are actively phagocytic, and pharmacological inhibition of phagocytosis disrupts scar clearance and regeneration. Second, B cells recruited from 7 days post-injury promote cardiomyocyte cell progression into mitosis, and their inhibition with Acalabrutinib significantly impairs cardiomyocyte proliferation and regeneration. This B cell-dependent mechanism is conserved in zebrafish. Our findings reveal two independent late immune mechanisms distinguishing regenerative from non-regenerative cardiac repair, offering insights for potential therapeutic strategies to enhance heart regeneration in mammals.
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BibTeX
@article{sengul2026absence,
title = {{Absence of a prolonged macrophage and B cell response inhibits heart regeneration in the Mexican cavefish.}},
author = {Esra Sengul and Helen G Potts and Ryan D Carter and William T Stockdale and Laura Bevan and Maria Nozdrina and Jun Ying and Konstantinos Lekkos and Rita Alonaizan and Zhilian Hu and Abigail Goodship and Lucy O'Byrne and Madeleine E Lemieux and Rebecca Richardson and Mathilda T M Mommersteeg},
journal = {Nature communications},
year = {2026},
month = sep,
doi = {10.1038/s41467-026-77725-4},
url = {https://europepmc.org/article/MED/42897151},
note = {CC BY},
}
RIS
TY - JOUR
TI - Absence of a prolonged macrophage and B cell response inhibits heart regeneration in the Mexican cavefish.
AU - Esra Sengul
AU - Helen G Potts
AU - Ryan D Carter
AU - William T Stockdale
AU - Laura Bevan
AU - Maria Nozdrina
AU - Jun Ying
AU - Konstantinos Lekkos
AU - Rita Alonaizan
AU - Zhilian Hu
AU - Abigail Goodship
AU - Lucy O'Byrne
AU - Madeleine E Lemieux
AU - Rebecca Richardson
AU - Mathilda T M Mommersteeg
PY - 2026
DA - 2026/09/17
JO - Nature communications
DO - 10.1038/s41467-026-77725-4
UR - https://europepmc.org/article/MED/42897151
AB - A balanced immune response after cardiac injury is crucial to successful heart regeneration, but knowledge of what distinguishes a regenerative from a scarring response is still limited. The Mexican cavefish Astyanax mexicanus provides a unique comparative model to study heart regeneration and scarring within a single species. Astyanax surface-dwelling fish are capable of heart regeneration, whereas, like the human heart, their cave-dwelling Pachón counterparts form a permanent scar. Using single-cell transcriptomics and immune perturbations, we identify two distinct and largely sequential immune mechanisms driving regeneration in surface fish. First, late-present macrophages are actively phagocytic, and pharmacological inhibition of phagocytosis disrupts scar clearance and regeneration. Second, B cells recruited from 7 days post-injury promote cardiomyocyte cell progression into mitosis, and their inhibition with Acalabrutinib significantly impairs cardiomyocyte proliferation and regeneration. This B cell-dependent mechanism is conserved in zebrafish. Our findings reveal two independent late immune mechanisms distinguishing regenerative from non-regenerative cardiac repair, offering insights for potential therapeutic strategies to enhance heart regeneration in mammals.
SN - 2041-1723
ER -