Single-cell RNA sequencing profiling of mouse cardiac cells in response to retinoic acid

Area of Science:

• Developmental biology
• Cardiovascular research
• Toxicology

Background:

• Congenital heart disease (CHD) is a leading cause of mortality related to birth defects.
• Environmental factors play a significant role in the multifactorial nature of CHD.
• Understanding the cellular and molecular mechanisms of cardiac malformation is crucial for developing interventions.

Purpose of the Study:

• To investigate the impact of all-trans retinoic acid (RA) on cardiac development using a mouse model.
• To elucidate the cellular and molecular changes in the developing heart following RA exposure.
• To identify specific cell populations and molecular pathways affected by RA during heart development.

Main Methods:

• Administration of a single dose of all-trans retinoic acid (RA) to pregnant mice at embryonic day 8.5 (E8.5) to create a CHD model.
• Single-cell RNA sequencing (scRNA-seq) of cardiac cells from E8.5 to E17.5.
• Analysis of gene expression patterns and cell subpopulations affected by RA exposure.

Main Results:

• RA significantly impacted cardiomyocyte (CM) subpopulations, notably reducing Tdgf1 expression in outflow tract CMs at E9.0.
• RA influenced endocardial-to-mesenchymal transition by decreasing Stmn2 levels, potentially affecting valve development.
• RA altered the metabolic patterns and promoted differentiation potential of epicardial cells at E11.5.

Conclusions:

• RA exposure during critical developmental windows induces specific cellular and molecular alterations in the developing heart.
• These findings provide valuable insights into the mechanisms underlying RA-induced cardiac malformations.
• The study offers a foundation for developing preventive and therapeutic strategies for congenital heart diseases.