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IGFBPs mediate IGF-1’s functions in retinal lamination and photoreceptor development during pluripotent stem cell differentiation to retinal organoids

Lookup NU author(s): Dr Darin Zerti, Marina Moya-Molina, Dr Birthe HilgenORCiD, Dr Roman BauerORCiD, Professor Majlinda LakoORCiD



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


Development of the retina is regulated by growth factors such as Insulin-like growth factors 1 and 2 (IGF-1/2), which coordinate proliferation, differentiation and maturation of the neuroepithelial precursors cells. In the circulation, IGF-1/2 are transported by the insulin growth factor binding proteins (IGFBPs) family members. IGFBPs can impact positively and negatively on IGF-1, by making it available or sequestering IGF-1 to or from its receptor. In this study, we investigated the expression of IGFBPs and their role in generation of human retinal organoids from human pluripotent stem cells, showing a dynamic expression pattern suggestive of different IGFBPs being employed in stage-specific manner to mediate IGF-1 functions. Our data show that IGF-1 addition to culture media facilitated the generation of retinal organoids displaying the typical laminated structure and photoreceptor maturation. The organoids cultured in the absence of IGF-1, lacked the typical laminated structure at the early stages of differentiation and contained significantly less photoreceptors and more retinal ganglion cells at the later stages of differentiation, confirming the positive effects of IGF-1 on retinal lamination and photoreceptor development. The organoids cultured with the IGFBP inhibitor (NBI-31772) and IGF-1 showed lack of retinal lamination at the early stages of differentiation, an increased propensity to generate horizontal cells at mid-stages of differentiation and reduced photoreceptor development at the later stages of differentiation. Together these data suggest that IGFBPs enables IGF-1’s role in retinal lamination and photoreceptor development in a stage-specific manner.

Publication metadata

Author(s): Zerti D, MoyaMolina M, Dorgau B, Mearns S, Bauer R, Alaama J, Lako M

Publication type: Article

Publication status: Published

Journal: Stem Cells

Year: 2021

Volume: 39

Issue: 4

Pages: 458-466

Print publication date: 01/04/2021

Online publication date: 14/01/2021

Acceptance date: 10/01/2021

Date deposited: 07/11/2023

ISSN (print): 1066-5099

ISSN (electronic): 1549-4918

Publisher: Wiley


DOI: 10.1002/stem.3331


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Funder referenceFunder name
Engineering and Physical Sciences Research Council of the United Kingdom
GR595RETINA UK (Formerly known as British Retinitis Pigmentosa Society)
Medical Research Council of the United Kingdom
MR/N015037/1Medical Research Council (MRC)
Retina UK