Regulation of WNT Signaling by VSX2 During Optic Vesicle Patterning in Human Induced Pluripotent Stem Cells

Capowski, E.E. ; Wright, L.S. ; Liang, K. ; Phillips, M.J. ; Wallace, K. ; Petelinsek, A. ; Hagstrom, A. ; Pinilla, I. (Universidad de Zaragoza) ; Borys, K. ; Lien, J. ; Min, J.H. ; Keles, S. ; Thomson, J.A. ; Gamm, D.M.

Resumen: Few gene targets of Visual System Homeobox 2 (VSX2) have been identified despite its broad and critical role in the maintenance of neural retina (NR) fate during early retinogenesis. We performed VSX2 ChIP-seq and ChIP-PCR assays on early stage optic vesicle-like structures (OVs) derived from human iPS cells (hiPSCs), which highlighted WNT pathway genes as direct regulatory targets of VSX2. Examination of early NR patterning in hiPSC-OVs from a patient with a functional null mutation in VSX2 revealed mis-expression and upregulation of WNT pathway components and retinal pigmented epithelium (RPE) markers in comparison to control hiPSCOVs. Furthermore, pharmacological inhibition of WNT signaling rescued the early mutant phenotype, whereas augmentation of WNT signaling in control hiPSC-OVs phenocopied the mutant. These findings reveal an important role for VSX2 as a regulator of WNT signaling and suggest that VSX2 may act to maintain NR identity at the expense of RPE in part by direct repression of WNT pathway constituents.

Idioma: Inglés

DOI: 10.1002/stem.2414

Año: 2016

Publicado en: STEM CELLS 34, 11 (2016), 2625-2634
ISSN: 1066-5099

Factor impacto JCR: 5.599 (2016)

Categ. JCR: BIOTECHNOLOGY & APPLIED MICROBIOLOGY rank: 16 / 160 = 0.1 (2016) - Q1 - T1
Categ. JCR: CELL BIOLOGY rank: 43 / 189 = 0.228 (2016) - Q1 - T1
Categ. JCR: CELL & TISSUE ENGINEERING rank: 4 / 21 = 0.19 (2016) - Q1 - T1
Categ. JCR: ONCOLOGY rank: 37 / 217 = 0.171 (2016) - Q1 - T1
Categ. JCR: HEMATOLOGY rank: 12 / 70 = 0.171 (2016) - Q1 - T1

Factor impacto SCIMAGO: 2.971 - Cell Biology (Q1) - Molecular Medicine (Q1) - Medicine (miscellaneous) (Q1) - Developmental Biology (Q1)

Tipo y forma: Artículo (Versión definitiva)

Área (Departamento): Área Oftalmología (Dpto. Cirugía,Ginecol.Obstetr.)