Transcriptional landscape of neonatal heart regeneration

Transcriptional landscape of neonatal heart regeneration

Adult mammalian heart cells cannot regenerate following injuries such as heart attacks. In contrast, neonatal mouse hearts can regenerate following injury, but only during the first week after birth, and the basis of this ability is poorly understood.

Researchers examined gene expression and chromatin landscapes, as well as response to myocardial infarction (MI), in regenerative and nonregenerative mouse hearts. MI triggered distinct responses in expression of genes related to immunity in 1-day-old and 8-day-old mouse hearts, as measured by transcription and chromatin activation and deactivation.

One of the genes preferentially expressed in 1-day-old mouse hearts encoded a macrophage-secreted factor, CCL24, which promoted proliferation of neonatal rat heart cells in vitro. The authors further identified a set of genes that were expressed in the heart during embryonic development and early neonatal stages, when hearts were capable of regeneration, but were silenced in adults.

One of these genes encoded the RNA-binding protein IGF2BP3, and 8-day-old mouse hearts overexpressing this protein exhibited enhanced post-MI regeneration and cardiac function, compared with controls.

According to the authors, neonatal hearts may exhibit a unique immune response to injury and retain an active developmental gene program, which together promote heart regeneration.