Mapping of the Developmental Atlas of the Visual System and Research on Embryonic Neurogenesis Phenomena

Condition(s) studied

Investigational drug(s) / intervention(s)

Tissue collection and multi-omics sequencing analysis: This observational study collects discarded human embryonic ocular and brain tissues from patients undergoing clinically indicated termination of pregnancy, with gestational age ranging from 9 to 40 weeks. We separate retinal, visual cortex and high-order cognitive cortex tissues, then perform single-cell multi-omics sequencing including transcriptome, chromatin accessibility and proteome profiling. The data is used to explore retinal neurogenesis, neuronal developmental trajectories and multi-modal cell atlas of embryonic visual system, without any clinical intervention on participants.

Study summary

This research studies how nerve cells in the human embryonic retina, visual brain regions, and brain areas responsible for higher cognitive functions grow, develop, and form interconnected functional networks.

Eye tissue, visual brain tissue, and other brain tissue linked to advanced cognitive functions will be collected from embryos whose pregnancies were terminated due to medical conditions or illnesses. High-throughput single-cell and single-nucleus sequencing will be utilized to map gene activity patterns and developmental growth pathways of retinal nerve cells.

Multiple testing tools will be combined to analyze these brain and retinal cells: Patch-seq (single-cell patch-clamp sequencing), high-density microelectrode arrays (MEA), and two-photon calcium imaging. With these tools, systematic measurements will be performed on the electrical activity, physical shape, synaptic connection patterns, and signal coding functions of neurons in the retina and visual brain regions. Multi-modal tissue maps and a public database will be constructed to store all collected research data.

Immunofluorescence staining will also be applied to compare structural differences and nerve fiber connections between visual brain regions and higher cognitive brain areas. The regenerative capacity and neuron formation process of embryonic brain stem cells, as well as the migration paths of developing neurons, will be tracked.

Overall, this study aims to fully uncover the neural foundation of visual signal processing, and identify the molecular regulatory networks that control nerve tissue development during the embryonic stage.

Eligibility

Primary outcome measure(s)

• Single-cell transcriptomic atlas and developmental trajectory of embryonic retinal and visual cortical neurons — Day 1 of tissue collection
  Perform single-cell RNA sequencing on human embryonic eye and brain tissues from abnormal developmental group and normal control group. Identify all cell subtypes in retina and visual-associated cognitive cortex, reconstruct continuous developmental trajectory of retinal neurogenesis and visual cortical neurons, and compare neuronal subtype distribution differences between the two groups.
• Genome-wide chromatin open regions in embryonic visual tissues — Day 1 of tissue collection
  Genome-wide chromatin open regions are detected via snATAC-seq on embryonic ocular and brain tissues from case and control groups.
• Differential chromatin accessibility between normal and malformed embryonic visual tissues — Day 1 of tissue collection
  Differential chromatin accessibility signals are identified via integrated analysis of snATAC-seq and scRNA-seq data from embryonic ocular and brain tissues.
• Candidate pathogenic genes underlying embryonic visual developmental abnormalities — Day 1 of tissue collection
  Genes linked to abnormal embryonic visual development are screened based on differential chromatin and transcriptomic profiles.

Trial sites (1)

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