Pluto Bioinformatics

GSE150521: -catenin drives distinct transcriptional networks in proliferative and non-proliferative cardiomyocytes

Bulk RNA sequencing

The inability of the adult mammalian heart to regenerate represents a fundamental barrier in heart failure management. In contrast, the neonatal heart retains a transient regenerative capacity, but the underlying mechanisms are not fully understood. Wnt/-catenin signaling has been suggested as a key cardio-regenerative pathway. Here, we show that Wnt/-catenin signaling potentiates neonatal mouse cardiomyocyte proliferation in vivo and immature human pluripotent stem cell-derived cardiomyocyte (hPSC-CM) proliferation in vitro. In contrast, Wnt/-catenin signaling in adult mice is cardioprotective but fails to induce cardiomyocyte proliferation. Transcriptional profiling of neonatal mouse and hPSC-CM revealed a core Wnt/-catenin-dependent transcriptional network governing cardiomyocyte proliferation. In contrast, -catenin failed to re-engage this proliferative gene network in the adult heart, which instead reverted to a neonatal-like glycolytic program. These findings suggest that Wnt/-catenin drives distinct transcriptional networks in regenerative and non-regenerative cardiomyocytes, which may contribute towards the inability of the adult heart to regenerate following injury. SOURCE: James Hudson (James.Hudson@QIMRBerghofer.edu.au) - Cardiac Bioengineering Laboratory QIMR Berghofer Medical Research Institute