Human iPSC differentiation to retinal organoids in response to IGF1 and BMP4 activation is line- and method-dependent

Chichagova, Valeria, Hilgen, Gerrit, Ghareeb, Ali, Georgiou, Maria, Carter, Madeleine, Sernagor, Evelyne, Lako, Majlinda and Armstrong, Lyle (2020) Human iPSC differentiation to retinal organoids in response to IGF1 and BMP4 activation is line- and method-dependent. Stem Cells, 38 (2). pp. 195-201. ISSN 1066-5099

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Official URL: https://doi.org/10.1002/stem.3116

Abstract

Induced pluripotent stem cell (iPSC)‐derived retinal organoids provide a platform to study human retinogenesis, disease modeling, and compound screening. Although retinal organoids may represent tissue structures with greater physiological relevance to the in vivo human retina, their generation is not without limitations. Various protocols have been developed to enable development of organoids with all major retinal cell types; however, variability across iPSC lines is often reported. Modulating signaling pathways important for eye formation, such as those involving bone morphogenetic protein 4 (BMP4) and insulin‐like growth factor 1 (IGF1), is a common approach used for the generation of retinal tissue in vitro. We used three human iPSC lines to generate retinal organoids by activating either BMP4 or IGF1 signaling and assessed differentiation efficiency by monitoring morphological changes, gene and protein expression, and function. Our results showed that the ability of iPSC to give rise to retinal organoids in response to IGF1 and BMP4 activation was line‐ and method‐dependent. This demonstrates that careful consideration is needed when choosing a differentiation approach, which would also depend on overall project aims.

Item Type: Article
Uncontrolled Keywords: differentiation, induced pluripotent stem cells, organoids, retina
Subjects: C400 Genetics
C700 Molecular Biology, Biophysics and Biochemistry
Department: Faculties > Health and Life Sciences > Applied Sciences
Depositing User: Elena Carlaw
Date Deposited: 11 May 2020 15:59
Last Modified: 11 May 2020 16:15
URI: http://nrl.northumbria.ac.uk/id/eprint/43068

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