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

Valeria Chichagova, Gerrit Hilgen, Ali Ghareeb, Maria Georgiou, Madeleine Carter, Evelyne Sernagor, Majlinda Lako, Lyle Armstrong*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)
8 Downloads (Pure)

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.

Original languageEnglish
Pages (from-to)195-201
Number of pages7
JournalStem Cells
Volume38
Issue number2
Early online date30 Dec 2019
DOIs
Publication statusPublished - 1 Feb 2020
Externally publishedYes

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