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Single-cell transcriptomic profiling of rat iridocorneal angle at perinatal stages: Revisiting the development of
Yunsheng Qiao1, Chen Tan1, Junyi Lai1
1Department of Ophthalmology & Visual Science, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, 200031, China; NHC Key Laboratory of Myopia, Chinese Academy of Medical Sciences, And Shanghai Key Laboratory of Visual Impairment and Restoration (Fudan University), Shanghai, 200031, China.
Insights
This study maps the periocular mesenchyme (POM) cell development, revealing key genes and networks crucial for anterior eye and iridocorneal angle (ICA) formation. Findings offer insights into normal development and anterior segment dysgenesis (ASD).
Area of Science:
- Developmental biology
- Ophthalmology
- Genomics
Background:
- The periocular mesenchyme (POM) is vital for anterior eye segment structures, but its development and regulatory mechanisms are poorly understood.
- Malformations in POM lead to anterior segment dysgenesis (ASD) and iridocorneal angle (ICA) abnormalities.
Purpose of the Study:
- To comprehensively analyze the transcriptional profile of the POM during perinatal development.
- To identify key genes and regulatory networks governing cell-fate decisions in anterior eye and ICA development.
- To provide a reference for understanding normal development and ASD pathogenesis.
Main Methods:
- Single-cell RNA sequencing of rat anterior ocular samples across five perinatal stages.
- Time-series analysis of transcriptomic data from 59,416 cells.
- Validation of in silico findings using immunostaining.
Main Results:
- Identified five POM subclusters with distinct molecular signatures and developmental trajectories.
- Revealed a significant transcriptional shift in POM cells around birth, coinciding with ICA anatomical changes.
- Uncovered key driver genes, gene modules, regulon network switches, and cellular crosstalk during POM maturation.
- Mapped ASD-relevant genes to the single-cell atlas, showing distinct expression patterns.
Conclusions:
- This study provides a detailed transcriptomic blueprint of normal POM and ICA development.
- The findings offer valuable insights into the molecular mechanisms underlying ASD.
- This resource will aid future research into anterior eye development and related disorders.
Abstract:
The periocular mesenchyme (POM) gives rise to key structures in the ocular anterior segment, and its malformation leads to anterior segment dysgenesis (ASD) with iridocorneal angle (ICA) abnormalities. However, the transcriptional profile of the POM and the regulatory mechanisms governing cell-fate decision during anterior eye and ICA development remain poorly understood. In this study, we performed a comprehensive time-series analysis by sequencing rat anterior ocular samples collected at five consecutive perinatal stages: embryonic days 16.5 and 18.5, the day of birth, and postnatal days 4 and 8, at the single-cell level and validated a portion of in silico findings with immunostaining. High-quality transcriptomes were obtained from 59,416 cells with diverse embryonic origins. A prominent transcriptional shift was observed in POM cells, coinciding with anatomical alterations around the ICA shortly after birth. We illustrated the molecular signatures of five POM subclusters while tracing their developmental trajectories. Additionally, we identified key driver genes, as well as cell type-specific and stage-wise gene modules underlying lineage specification. Furthermore, the switch of regulon network and cellular crosstalk associated with POM maturation were unveiled. Lastly, we mapped ASD-relevant genes to this single-cell atlas, revealing distinct expression patterns. Collectively, this study provides a transcriptomic blueprint for understanding normal POM and ICA development, as well as a valuable reference for future research into ASD pathogenesis.
