Researchers at the University of Southern California identified a gene that may help regenerate damaged heart tissue after a heart attack. in the journal Nature Genetics.

Declining Regenerative Heart Cells with Age
At birth, we have many mononuclear diploid cardiomyocytes (MNDCMs), heart muscle cells with strong regenerative power. As we age, MNDCM levels drop sharply. By the time we reach the age when heart attacks become common, most of us have very few MNDCMs left—and a limited ability to repair heart damage.

Michaela Patterson and her USC team looked for ways to reverse this decline. They found that some adult mice had fewer than 2 percent MNDCMs, while others had about 10 percent. Mice with more MNDCMs regenerated heart tissue far better after injury.
With support from CIRM, the team conducted a genome‑wide association study to identify genetic factors linked to higher MNDCM levels. They pinpointed one gene, Tnni3k, as a key regulator.

Turning off Tnni3k in mice increased MNDCM numbers and improved heart regeneration. Activating the gene in zebrafish reduced MNDCM levels and impaired their ability to heal heart damage.

Potential Path to Future Therapies
Henry Sucov, the study’s senior author, says the findings lay early groundwork for human applications:

“The activity of Tnni3k can be modulated by small molecules, which could be developed into prescription drugs.

These molecules could gradually increase the number of regenerative cells in the adult heart. That would improve the heart’s ability to repair damage and potentially reducing the risk of heart failure.”

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