Medical College of Wisconsin
CTSIResearch InformaticsREDCap

Examination of an iPSC model of human eye development reveals progressive emergence of critical embryonic cell types. Sci Rep 2025 Jul 02;15(1):23009

Date

07/02/2025

Pubmed ID

40596144

Pubmed Central ID

PMC12214497

DOI

10.1038/s41598-025-06602-9

Scopus ID

2-s2.0-105010100561 (requires institutional sign-in at Scopus site)   2 Citations

Abstract

Human iPSC-derived models currently used in eye research usually replicate later events of tissue differentiation rather than early steps involving concurrent development of diverse embryonic cell types. Here we present a multi-timepoint morphological and transcriptomic analysis of a 2D model mirroring the early stages of human whole eye development, self-formed ectodermal autonomous multi-zone (SEAM) of ocular cells. SEAM cultures maintained a reproducible growth profile over the standard 28-day differentiation process with quantifiable morphological changes accompanying generation of key ocular cell types over time. Bulk and single-cell RNA-seq analyses at Days 0, 14 and 28 identified dynamic transcriptomic changes indicative of the emerging cell types, including rare stem cell-like populations analogous to those comprising the ciliary marginal zone, transit-amplifying cells, limbal epithelial stem cells, and corneal stromal stem cells. Integrated developmental trajectory analysis highlighted intermediate differentiation states underlying SEAM maturation. Cluster-specific interrogation of eye disease-associated genes demonstrated dynamic temporal patterns and enrichment in relevant developing cell types. These analyses establish a comprehensive baseline of SEAM formation, supporting the potential of the model to facilitate mechanistic studies of genetic variants that may uniquely impact humans, thus improving the success rate in resolving cases presenting with a broad range of developmental eye phenotypes.

Author List

Replogle MR, Ma X, Lin CW, Semina EV

Authors

Chien-Wei Lin PhD Associate Professor in the Data Science Institute department at Medical College of Wisconsin
Maria R. Replogle Research Scientist I in the Ophthalmology department at Medical College of Wisconsin
Elena V. Semina PhD Chief, Professor in the Ophthalmology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Cell Differentiation
Eye
Gene Expression Profiling
Humans
Induced Pluripotent Stem Cells
Models, Biological
Single-Cell Analysis
Transcriptome