Zebrafish Protein Unlocks Dormant Genes for Heart Repair

Researchers discovered that the protein Hmga1 plays a key role in heart regeneration in zebrafish.

News

Published: January 3, 2025

| Original story from the Hubrecht Institute

Credit: iStock

Listen with

Speechify

0:00

Thank you. Listen to this article using the player above. ✖

Want to listen to this article for FREE?

Complete the form below to unlock access to ALL audio articles.

Read time: 2 minutes

Researchers from the Bakkers group at the Hubrecht Institute have successfully repaired damaged mouse hearts using a protein from zebrafish. They discovered that the protein Hmga1 plays a key role in heart regeneration in zebrafish. In mice, this protein was able to restore the heart by activating dormant repair genes without causing side effects, such as heart enlargement. This study, supported by the Dutch Heart Foundation and Hartekind Foundation, marks an important step toward regenerative therapies to prevent heart failure. The findings were published in Nature Cardiovascular Research on January 2, 2025.

After a heart attack, the human heart loses millions of muscle cells that cannot regrow. This often leads to heart failure, where the heart struggles to pump blood effectively. Unlike humans, zebrafish grow new heart muscle cells: they have a regenerative capacity. When a zebrafish heart is damaged, it can fully restore its function within 60 days. “We don’t understand why some species can regenerate their hearts after injury while others cannot”, explains Jeroen Bakkers, the study’s leader. “By studying zebrafish and comparing them to other species, we can uncover the mechanisms of heart regeneration. This could eventually lead to therapies to prevent heart failure in humans.”

Want more breaking news?

Subscribe to Technology Networks’ daily newsletter, delivering breaking science news straight to your inbox every day.

Subscribe for FREE

A protein that repairs damage

The research team identified a protein that enables heart repair in zebrafish. “We compared the zebrafish heart to the mouse heart, which, like the human heart, cannot regenerate”, says Dennis de Bakker, the study’s first author. “We looked at the activity of genes in damaged and healthy parts of the heart”, he explains. “Our findings revealed that the gene for the Hmga1 protein is active during heart regeneration in zebrafish but not in mice. This showed us that Hmga1 plays a key role in heart repair.” Typically, the Hmga1 protein is important during embryonic development when cells need to grow a lot. However, in adult cells, the gene for this protein is turned off.

Clearing ‘roadblocks’

The researchers investigate how the Hmga1 protein works. “We discovered that Hmga1 removes molecular ‘roadblocks’ on chromatin”, explains Mara Bouwman, co-first author. Chromatin is the structure that packages DNA. When it is tightly packed, genes are inactive. When it unpacks, genes can become active again. “Hmga1 clears the way, so to say, allowing dormant genes to get back to work”, she adds.

What’s next?

These findings open doors for safe, targeted regenerative therapies, but there is still much work to do. “We need to refine and test the therapy further before it can be brought to the clinic”, says Bakkers. “The next step is to test whether the protein also works on human heart muscle cells in culture. We are collaborating with UMC Utrecht for this, and in 2025, the Summit program (DRIVE-RM) will begin to explore heart regeneration further.”

Reference: Bouwman M, de Bakker DEM, Honkoop H, et al. Cross-species comparison reveals that Hmga1 reduces H3K27me3 levels to promote cardiomyocyte proliferation and cardiac regeneration. Nat Cardiovasc Res. 2025. doi: 10.1038/s44161-024-00588-9

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source. Our press release publishing policy can be accessed here.

Cell Science