| RRC ID |
85248
|
| 著者 |
Replogle MR, Ma X, Lin CW, Semina EV.
|
| タイトル |
Examination of an iPSC model of human eye development reveals progressive emergence of critical embryonic cell types.
|
| ジャーナル |
Sci Rep
|
| 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.
|
| 巻・号 |
15(1)
|
| ページ |
23009
|
| 公開日 |
2025-7-2
|
| DOI |
10.1038/s41598-025-06602-9
|
| PII |
10.1038/s41598-025-06602-9
|
| PMID |
40596144
|
| PMC |
PMC12214497
|
| MeSH |
Cell Differentiation
Eye* / cytology
Eye* / embryology
Gene Expression Profiling
Humans
Induced Pluripotent Stem Cells* / cytology
Induced Pluripotent Stem Cells* / metabolism
Models, Biological
Single-Cell Analysis
Transcriptome
|
| IF |
3.998
|
| リソース情報 |
| ヒト・動物細胞 |
201B7(HPS0063) |
