PUBLICATION
ALPK2 Promotes Cardiogenesis in Zebrafish and Human Pluripotent Stem Cells
- Authors
- Hofsteen, P., Robitaille, A.M., Strash, N., Palpant, N., Moon, R.T., Pabon, L., Murry, C.E.
- ID
- ZDB-PUB-180612-3
- Date
- 2018
- Source
- iScience 2: 88-100 (Journal)
- Registered Authors
- Moon, Randall T.
- Keywords
- none
- MeSH Terms
- none
- PubMed
- 29888752 Full text @ iScience
Citation
Hofsteen, P., Robitaille, A.M., Strash, N., Palpant, N., Moon, R.T., Pabon, L., Murry, C.E. (2018) ALPK2 Promotes Cardiogenesis in Zebrafish and Human Pluripotent Stem Cells. iScience. 2:88-100.
Abstract
Cardiac development requires coordinated biphasic regulation of the WNT/β-catenin signaling pathway. By intersecting gene expression and loss-of-function siRNA screens we identified Alpha Protein Kinase 2 (ALPK2) as a candidate negative regulator of WNT/β-catenin signaling in cardiogenesis. In differentiating human embryonic stem cells (hESCs), ALPK2 is highly induced as hESCs transition from mesoderm to cardiac progenitors. Using antisense knockdown and CRISPR/Cas9 mutagenesis in hESCs and zebrafish, we demonstrate that ALPK2 promotes cardiac function and cardiomyocyte differentiation. Quantitative phosphoproteomics, protein expression profiling, and β-catenin reporter assays demonstrate that loss of ALPK2 led to stabilization of β-catenin and increased WNT signaling. Furthermore, cardiac defects attributed to ALPK2 depletion can be rescued in a dose-dependent manner by direct inhibition of WNT signaling through the small molecule XAV939. Together, these results demonstrate that ALPK2 regulates β-catenin-dependent signaling during developmental commitment of cardiomyocytes.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping