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

Обзор

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.

Вмешательства

• Другое 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-m

Первичные конечные точки

• Single-cell transcriptomic atlas and developmental trajectory of embryonic retinal and visual cortical neurons [Срок оценки: Day 1 of tissue collection]
• Genome-wide chromatin open regions in embryonic visual tissues [Срок оценки: Day 1 of tissue collection]
• Differential chromatin accessibility between normal and malformed embryonic visual tissues [Срок оценки: Day 1 of tissue collection]
• Candidate pathogenic genes underlying embryonic visual developmental abnormalities [Срок оценки: Day 1 of tissue collection]

Вторичные конечные точки (5)

• Action potential firing patterns of embryonic visual neurons [Срок оценки: Day 1 of tissue collection]
• Synchronous electrical activity of embryonic neuronal networks [Срок оценки: Day 1 of tissue collection]
• Spatial expression localization of key visual development genes detected by RNAscope [Срок оценки: The day 1 of embryonic tissue collection after clinical termination of pregnancy]
• Differentially expressed proteins identified via global proteome sequencing [Срок оценки: Day 1 of tissue collection]
• Spatial localization and expression abundance of proteins via immunohistochemistry [Срок оценки: Day 1 of tissue collection]

Критерии участия

Критерии включения

• Abnormal group: Embryos with clinically confirmed embryonic developmental abnormalities requiring medical termination of pregnancy; intact retinal, visual and cognitive brain tissues available for snATAC-seq, scRNA-seq, electrophysiology, proteomics and RNAscope detection.

Normal group: Embryos confirmed free of any ocular and central nervous developmental defects by prenatal examination and anatomical observation; intact embryonic ocular and brain tissues meeting all experimental detection standards.

All sample donors have signed written informed consent authorizing the use of residual embryonic tissues for scientific research, with no monetary compensation involved.

Критерии исключения

• Embryonic ocular or brain tissues with severe necrosis, structural damage or microbial contamination that cannot support multi-omics and functional experiments.

Donors who withdraw or refuse the consent for tissue research use. Samples with irregular collection, transportation or cryopreservation procedures resulting in tissue degradation and failure to meet experimental requirements.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Модель наблюдения

Случай-контроль

Центры проведения

Китай · 1 центр

• Zhongshan Ophthalmic Center, Sun Yat-sen University — Гуанчжоу

Публикации

• Huang W, Xu Q, Liu F, Su J, Xiao D, Tang L, Hao ZZ, Liu R, Xiang K, Bi Y, Miao Z, Liu X, Liu Y, Liu S. Identification of TPBG-Expressing Amacrine Cells in DAT-tdTomato Mouse. Invest Ophthalmol Vis Sci. 2022 May 2;63(5):13. doi: 10.1167/iovs.63.5.13. PMID 35551574
• Huang W, Xu Q, Su J, Tang L, Hao ZZ, Xu C, Liu R, Shen Y, Sang X, Xu N, Tie X, Miao Z, Liu X, Xu Y, Liu F, Liu Y, Liu S. Linking transcriptomes with morphological and functional phenotypes in mammalian retinal ganglion cells. Cell Rep. 2022 Sep 13;40(11):111322. doi: 10.1016/j.celrep.2022.111322. PMID 36103830
• Chen X, Huang Y, Huang L, Huang Z, Hao ZZ, Xu L, Xu N, Li Z, Mou Y, Ye M, You R, Zhang X, Liu S, Miao Z. A brain cell atlas integrating single-cell transcriptomes across human brain regions. Nat Med. 2024 Sep;30(9):2679-2691. doi: 10.1038/s41591-024-03150-z. Epub 2024 Aug 2. PMID 39095595
• Wei JR, Xiao D, Tang L, Xu N, Liu R, Shen Y, Xu Z, Sang X, Ge J, Xiang M, Liu S. Neural cell isolation from adult macaques for high-throughput analyses and neurosphere cultures. Nat Protoc. 2023 Jun;18(6):1930-1957. doi: 10.1038/s41596-023-00820-z. Epub 2023 Apr 12. PMID 37045994

Идентификаторы

NCT: NCT07688538 · IIT2025136

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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