ALPK2 Promotes Cardiogenesis in Zebrafish and Human Pluripotent Stem Cells.

Area of Science:

• Developmental Biology
• Molecular Cardiology
• Stem Cell Biology

Background:

• Cardiac development relies on precise WNT/β-catenin signaling.
• Dysregulation of this pathway is linked to cardiac abnormalities.

Purpose of the Study:

• To identify novel regulators of WNT/β-catenin signaling during cardiogenesis.
• To investigate the role of Alpha Protein Kinase 2 (ALPK2) in heart development.

Main Methods:

• Intersected gene expression and siRNA screens to identify ALPK2.
• Utilized antisense knockdown and CRISPR/Cas9 in human embryonic stem cells (hESCs) and zebrafish.
• Performed quantitative phosphoproteomics, protein profiling, and reporter assays.

Main Results:

• ALPK2 is upregulated during cardiac progenitor specification in hESCs.
• ALPK2 depletion caused β-catenin stabilization and increased WNT signaling.
• ALPK2 deficiency impaired cardiac function and cardiomyocyte differentiation, which was rescued by WNT inhibition.

Conclusions:

• ALPK2 functions as a negative regulator of WNT/β-catenin signaling in cardiogenesis.
• ALPK2 is essential for promoting cardiac function and cardiomyocyte differentiation.
• ALPK2's role in regulating β-catenin signaling is critical for developmental commitment of cardiomyocytes.