Is zebrafish heart regeneration "complete"? Lineage-restricted cardiomyocytes proliferate to pre-injury numbers but some fail to differentiate in fibrotic hearts.

Is zebrafish heart regeneration "complete"? Lineage-restricted cardiomyocytes proliferate to pre-injury numbers but some fail to differentiate in fibrotic hearts.
Dev Biol. 2020 Dec 10;:
Authors: Bertozzi A, Wu CC, Nguyen PD, Vasudevarao MD, Mulaw MA, Koopman CD, de Boer TP, Bakkers J, Weidinger G
Abstract
Adult zebrafish are frequently described to be able to "completely" regenerate the heart. Yet, the extent to which cardiomyocytes lost to injury are replaced is unknown, since only indirect evidence for cardiomyocyte proliferation exists. We established stereological methods to quantify the number of cardiomyocytes at several time-points post cryoinjury. Intriguingly, after cryoinjuries that killed about 1/3 of the ventricular cardiomyocytes, pre-injury cardiomyocyte numbers were restored already within 30 days. Yet, many hearts retained small residual scars, and a subset of cardiomyocytes bordering these fibrotic areas remained smaller, lacked differentiated sarcomeric structures, and displayed defective calcium signaling. Thus, a subset of regenerated cardiomyocytes failed to fully mature. While lineage-tracing experiments have shown that regenerating cardiomyocytes are derived from differentiated cardiomyocytes, technical limitations have previously made it impossible to test whether cardiomyocyte trans-differentiation contributes to regeneration of non-myocyte cell lineages. Using Cre responder lines that are expressed in all m...

Source: Developmental Biology - December 10, 2020 Category: Biology Authors: Bertozzi A, Wu CC, Nguyen PD, Vasudevarao MD, Mulaw MA, Koopman CD, de Boer TP, Bakkers J, Weidinger G Tags: Dev Biol Source Type: research