Polycomb Group Protein CBX7 Represses Cardiomyocyte Proliferation Through Modulation of the TARDBP/RBM38 Axis

Area of Science:

• Cardiovascular Biology
• Cell Cycle Regulation
• Cardiac Regeneration

Background:

• Cardiomyocytes cease proliferation shortly after birth, a process poorly understood.
• Chromobox 7 (CBX7), a polycomb group protein, is known to regulate the cell cycle but its role in cardiomyocytes is unelucidated.

Purpose of the Study:

• To investigate the role of CBX7 in cardiomyocyte proliferation and cell cycle exit.
• To explore the potential of CBX7 as a target for cardiac regeneration therapies.

Main Methods:

• CBX7 expression was profiled in mouse hearts using qPCR, Western blotting, and immunohistochemistry.
• CBX7 was overexpressed or knocked down in neonatal mouse cardiomyocytes and in vivo models (constitutive and inducible conditional knockout mice).
• Cardiomyocyte proliferation was assessed using markers like Ki67 and phospho-histone 3; cardiac regeneration was studied in neonatal resection and adult myocardial infarction models.

Main Results:

• CBX7 expression increases significantly after birth in mouse hearts.
• CBX7 overexpression reduced neonatal cardiomyocyte proliferation, while its genetic inactivation increased proliferation and promoted cardiac regeneration in both neonatal and adult injured hearts.
• Mechanistically, CBX7 interacts with TARDBP and regulates its downstream target RBM38, which in turn affects cardiomyocyte proliferation.

Conclusions:

• CBX7 plays a critical role in directing cardiomyocyte cell cycle exit postnatally via regulation of TARDBP and RBM38.
• This study is the first to demonstrate CBX7's function in cardiomyocyte proliferation control.
• CBX7 emerges as a promising therapeutic target for enhancing cardiac regeneration.