Fosl1 is vital to heart regeneration upon apex resection in adult Xenopus tropicalis

npj Regenerative Medicine, 2021 · DOI: 10.1038/s41536-021-00146-y · Published: July 2, 2021

Cardiovascular Science Genetics Regenerative Medicine & Stem Cells

Simple Explanation

This research investigates heart regeneration in adult Xenopus tropicalis frogs after injury. The study found that the frogs could regenerate heart tissue through cardiomyocyte proliferation. The study identifies a gene, Fosl1, as a key factor in promoting cardiomyocyte proliferation during heart regeneration. Overexpression of Fosl1 promotes cell growth. The researchers modulated Fosl1 expression in vitro and in vivo, demonstrating its role in heart regeneration in both X. tropicalis and mouse models. Blocking Fosl1 function leads to defects in cardiomyocyte proliferation.

Study Duration

90 days

Participants

Adult Xenopus tropicalis, H9c2 cells, neonatal mice, adult mice

Evidence Level

Not specified

Key Findings

1
Cardiomyocyte proliferation greatly contributes to heart regeneration in adult X. tropicalis upon apex resection.
2
Fosl1 expression was dramatically upregulated in the early stage of heart injury in X. tropicalis.
3
Fosl1 interacts with JunB and promotes the expression of Cyclin-T1 (Ccnt1) during heart regeneration.

Research Summary

This study demonstrates that adult X. tropicalis can regenerate heart tissue after ventricular apex resection, primarily through cardiomyocyte proliferation. RNA-seq analysis identified Fosl1 as a key regulator, with its expression significantly upregulated in the early stages of heart injury. Fosl1 promotes cardiomyocyte proliferation and heart regeneration by interacting with JunB and promoting the expression of cell cycle regulators like Ccnt1.

Practical Implications

Potential therapeutic target

Fosl1 could be a therapeutic target for promoting heart regeneration in mammals.

Model for heart regeneration

X. tropicalis is a suitable model for studying adult heart regeneration due to its closer evolutionary relationship with mammals.

Understanding vertebrate heart regeneration

Fosl1 is critical for the regulation of vertebrate heart regeneration.

Study Limitations

1
CM labeling was mostly performed using whole-cell staining of CMs.
2
Cell fate tracing technology and nuclear staining of CMs should be used to support the conclusion in the future.
3
The study lacks specific Fosl1 antibody for X. tropicalis.

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