FOXK1 regulates Wnt signalling to promote cardiogenesis

Area of Science:

• Developmental Biology
• Genetics
• Molecular Biology

Background:

• Congenital heart disease (CHD) is a common genetic birth defect with significant morbidity and mortality.
• Understanding the regulators of cardiac progenitor cells and cardiogenesis is critical for addressing CHD.
• FOXK1, a forkhead transcription factor, is known to influence cell cycle and is present in cardiac development pathways.

Purpose of the Study:

• To define the essential role of FOXK1 in cardiovascular development.
• To investigate the regulatory mechanisms by which FOXK1 influences cardiogenesis.

Main Methods:

• Utilized a mouse embryoid body system with control and Foxk1 knockout (KO) embryonic stem cells.
• Employed flow cytometry, immunohistochemistry, cardiac beating assays, RNA sequencing (RNAseq), and ATAC-seq.
• Assessed cardiac Troponin T expression and cardiac contractility to evaluate differentiation.

Main Results:

• Foxk1 KO embryoid bodies showed perturbed cardiogenesis and a significant reduction in the cardiac molecular program.
• ATAC-seq revealed altered chromatin accessibility near key cardiac regulators in Foxk1 KO EBs.
• Absence of FOXK1 markedly impaired cardiac differentiation and contractility.

Conclusions:

• FOXK1 is an essential transcriptional and epigenetic regulator of cardiovascular development.
• FOXK1 functions by repressing the Wnt/β-catenin signaling pathway, thereby promoting cardiac progenitor cell development.