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ZIRC
ZFIN ID: ZDB-PUB-180612-3
ALPK2 Promotes Cardiogenesis in Zebrafish and Human Pluripotent Stem Cells
Hofsteen, P., Robitaille, A.M., Strash, N., Palpant, N., Moon, R.T., Pabon, L., Murry, C.E.
Date: 2018
Source: iScience 2: 88-100 (Journal)
Registered Authors: Moon, Randall T.
Keywords: none
MeSH Terms: none
PubMed: 29888752 Full text @ iScience
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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.
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