Open AccessIGFBPs mediate IGF‐1's functions in retinal lamination and photoreceptor development during pluripotent stem cell differentiation to retinal organoids
Author(s) -
Zerti Darin,
Molina Marina Moya,
Dorgau Birthe,
Mearns Sarah,
Bauer Roman,
AlAama Jumana,
Lako Majlinda
Publication year - 2021
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.3331
Subject(s) - biology , retinal , microbiology and biotechnology , cellular differentiation , retina , stem cell , retinal regeneration , organoid , induced pluripotent stem cell , neuroscience , genetics , regeneration (biology) , biochemistry , embryonic stem cell , gene
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 the generation of human retinal organoids from human pluripotent stem cells, showing a dynamic expression pattern suggestive of different IGFBPs being used in a 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 enable IGF‐1's role in retinal lamination and photoreceptor development in a stage‐specific manner.