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Cardiomyocyte proliferation is suppressed by ARID1A-mediated YAP inhibition during cardiac maturation

Cornelis J Boogerd1, Ilaria Perini2, Eirini Kyriakopoulou2

  • 1Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and University Medical Center Utrecht, Utrecht, Netherlands. K.boogerd@hubrecht.eu.

Nature Communications
|August 5, 2023
PubMed

Insights

Adult cardiomyocytes cannot regenerate due to a lack of proliferation. Arid1a, a chromatin remodeler, suppresses proliferation and promotes maturation, offering new avenues for cardiac repair research.

Area of Science:

  • Cardiology
  • Molecular Biology
  • Epigenetics

Background:

  • Adult cardiomyocyte proliferation is limited, hindering cardiac regeneration after injury.
  • Understanding the switch to a non-regenerative state is crucial for developing therapeutic strategies.

Purpose of the Study:

  • To investigate the role of Arid1a in regulating postnatal cardiomyocyte proliferation and maturation.
  • To elucidate the molecular mechanisms by which Arid1a controls cardiomyocyte cell cycle exit.

Main Methods:

  • Genome-wide transcriptome and epigenome analyses were performed.
  • Arid1a's interaction with YAP/TAZ and TEAD was assessed.
  • Arid1a's role was evaluated in a mouse model of ischemic heart disease.

Main Results:

  • Arid1a, a SWI/SNF complex subunit, suppresses cardiomyocyte proliferation and promotes maturation.
  • Arid1a facilitates DNA access for transcription factors driving cardiomyocyte maturation.
  • Arid1a directly inhibits YAP/TAZ, sequestering them from TEAD.
  • Inactivation of Arid1a post-ischemic injury enhances border zone cardiomyocyte proliferation.

Conclusions:

  • Arid1a is a key regulator of cardiomyocyte maturation and a critical suppressor of proliferation.
  • Targeting Arid1a may offer a novel strategy for promoting cardiac regeneration.

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