Single-cell transcriptomic analysis of corneal organoids during development.

Stem Cell Reports

Department of Ophthalmology, Stanford University School of Medicine, Stanford, CA, USA; Institute of Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA. Electronic address:

Published: December 2023


Category Ranking

98%

Total Visits

921

Avg Visit Duration

2 minutes

Citations

20

Article Abstract

Corneal organoids are useful tools for disease modeling and tissue transplantation; however, they have not yet been well studied during maturation. We characterized human iPSC-derived corneal organoids at 1, 2, 3, and 4 months of development using single-cell RNA sequencing to determine the cellular heterogeneity at each stage. We found pluripotent cell clusters committed to epithelial cell lineage at 1 month; early corneal epithelial, endothelial, and stromal cell markers at 2 months; keratocytes as the largest cell population at 3 months; and a large epithelial cell population at 4 months. We compared organoid to fetal corneal development at different stages and found that 4-month organoids closely resemble the corneal cellular complexity of the fetal (16 post conception week) and adult cornea. Using RNA velocity trajectory analysis, we found that less differentiated cells appear to give rise to corneal epithelial cells during development.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10724212PMC
http://dx.doi.org/10.1016/j.stemcr.2023.10.022DOI Listing

Publication Analysis

Top Keywords

corneal organoids
12
epithelial cell
8
corneal epithelial
8
cell population
8
corneal
7
cell
5
single-cell transcriptomic
4
transcriptomic analysis
4
analysis corneal
4
organoids
4

Similar Publications

The cornea, a transparent tissue composed of multiple layers, allows light to enter the eye. Several single-cell RNA-seq (scRNA-seq) analyses have been performed to explore the cell states and to understand the cellular composition of the human cornea. However, inconsistences in cell state annotations between these studies complicate the application of these findings in corneal studies.

View Article and Find Full Text PDF

During eye development, surface ectoderm cells that express PAX6 differentiate into corneal, limbal and conjunctival epithelia. However, several aspects of this differentiation process -- such as the developmental origin of the limbal epithelium and the mechanisms that underlie PAX6-mediated lineage specification -- are not properly understood. To explore these issues, we used single-cell RNA sequencing to study ocular surface epithelial cells derived from human induced pluripotent stem cells.

View Article and Find Full Text PDF

Stem cell therapy in regenerative medicine has a scope for treating ocular diseases. Stem cell therapy aims to repair damaged tissue and restore vision. The present review focuses on the advancements in stem cell therapies for ocular disorders, their mechanism of action, and clinical applications while addressing some outstanding challenges.

View Article and Find Full Text PDF

Introduction: Patients with limbal dysfunction, which occurs when corneal epithelial stem cells are depleted, require the transplantation of donor corneal epithelial stem cells or donor-independent cell sources. This study aimed to establish organoids with limbal epithelial progenitor cell function from the central cornea, where stem cells do not reside . We confirmed the regenerative capacity of organoids in a rabbit limbal deficiency model.

View Article and Find Full Text PDF

From bench to bedside: Developing CRISPR/Cas-based therapy for ocular diseases.

Pharmacol Res

March 2025

Department of Ophthalmology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China; Key Laboratory of Ocular Fundus Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College Hospital, Beijing 100730, China; Beijing Key Laboratory of Fund

Vision-threatening disorders, including both hereditary and multifactorial ocular diseases, necessitate innovative therapeutic approaches. The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated protein (Cas) has emerged as a promising tool for treating ocular diseases through gene editing and expression regulation. This system has contributed to the development of representative disease models, including animal models, organoids, and cell lines, thereby facilitating investigations into the pathogenesis of disease-related genes.

View Article and Find Full Text PDF