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

Lookup NU author(s): Dr Valeria Chichagova, Dr Gerrit HilgenORCiD, Dr Ali Ghareeb, Madeleine Carter, Professor Evelyne SernagorORCiD, Professor Majlinda LakoORCiD, Professor Lyle Armstrong



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Induced pluripotent stem cell (iPSC)-derived retinal organoids provide a platform to study human retinogenesis, disease modelling and compound screening. Whilst 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 signalling pathways important for eye formation, such as those involving bone morphogenetic protein 4 (BMP4) and insulin-like growth factor (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 signalling and assessed differentiation efficiency by monitoring morphological changes, gene and protein expression, and function. Our results showed that iPSC ability 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.

Publication metadata

Author(s): Chichagova V, Hilgen G, Ghareeb A, Gergiou M, Carter M, Sernagor E, Lako M, Armstrong L

Publication type: Article

Publication status: Published

Journal: Stem Cells

Year: 2020

Volume: 38

Issue: 2

Pages: 195-201

Print publication date: 01/02/2020

Online publication date: 13/11/2019

Acceptance date: 01/11/2019

Date deposited: 07/11/2019

ISSN (print): 1066-5099

ISSN (electronic): 1549-4918

Publisher: AlphaMed Press, Inc.


DOI: 10.1002/stem.3116


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Funder referenceFunder name
614620European Research Council (ERC)
GR595RETINA UK (Formerly known as British Retinitis Pigmentosa Society)
GR584RETINA UK (Formerly known as British Retinitis Pigmentosa Society)