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

NCT07688538 | Recruiting

• 1 other identifier: IIT2025136
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Neural Development; Retinal Anomalies; Embryonic Development

Keywords

retina; visual cortex; cognitive cortex; neurogenesis

Outcome Measures

Primary Outcomes (4)

• Single-cell transcriptomic atlas and developmental trajectory of embryonic retinal and visual cortical neurons

  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.

  Day 1 of tissue collection

• Genome-wide chromatin open regions in embryonic visual tissues

  Genome-wide chromatin open regions are detected via snATAC-seq on embryonic ocular and brain tissues from case and control groups.

  Day 1 of tissue collection

• Differential chromatin accessibility between normal and malformed embryonic visual tissues

  Differential chromatin accessibility signals are identified via integrated analysis of snATAC-seq and scRNA-seq data from embryonic ocular and brain tissues.

  Day 1 of tissue collection

• Candidate pathogenic genes underlying embryonic visual developmental abnormalities

  Genes linked to abnormal embryonic visual development are screened based on differential chromatin and transcriptomic profiles.

  Day 1 of tissue collection

Secondary Outcomes (5)

• Action potential firing patterns of embryonic visual neurons

  Day 1 of tissue collection

• Synchronous electrical activity of embryonic neuronal networks

  Day 1 of tissue collection

• Spatial expression localization of key visual development genes detected by RNAscope

  The day 1 of embryonic tissue collection after clinical termination of pregnancy

• Differentially expressed proteins identified via global proteome sequencing

  Day 1 of tissue collection

• Spatial localization and expression abundance of proteins via immunohistochemistry

  Day 1 of tissue collection

Study Arms (2)

Abnormal Group

Embryos with confirmed embryonic developmental abnormalities, gestational age 9-40 weeks, from patients receiving clinically indicated termination of pregnancy. Tissue collection and multi-omics sequencing analysis will be performed on ocular and brain tissues.

Other: Tissue collection and multi-omics sequencing analysis

Normal Group

Embryonic tissues derived from normally developing embryos with gestational age of 9 to 40 weeks, collected from pregnant women who voluntarily received clinically indicated termination of pregnancy. Ocular and brain tissues will be collected and subjected to multi-omics sequencing analysis consistent with the abnormal group.

Other: Tissue collection and multi-omics sequencing analysis

Interventions

Tissue collection and multi-omics sequencing analysis OTHER

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.

Abnormal Group; Normal Group

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

This study recruits pregnant patients undergoing termination of pregnancy at the Third Affiliated Hospital of Sun Yat-sen University, divided into an embryonic developmental abnormality group (Abnormal group) and a normal control group (Normal group), with a planned enrollment of 100 subjects per group. The gestational age of embryos ranges from 9 to 40 weeks. Two types of samples are included: retrospective cryopreserved specimens from the hospital biobank collected between January 2025 and January 2026 (20 cases per group, with donors having signed informed consent for specimen research use); and prospective fresh specimens collected between February 2026 and June 2027 (80 cases per group). All participants sign study-specific written informed consent.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sheng Liu: lead
• Third Affiliated Hospital, Sun Yat-Sen University: collaborator

Study Sites (1)

Zhongshan Ophthalmic Center, Sun Yat-sen University

Guangzhou, Guangdong, 510060, China

RECRUITING

Related Publications (4)

• 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 RESULT

• 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 RESULT

• 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 RESULT

• 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 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

Retained biospecimens are human embryonic ocular tissues and brain tissues collected from embryos after medical pregnancy termination with informed consent and ethical approval.

MeSH Terms

Interventions

Tissue Banks

Intervention Hierarchy (Ancestors)

Biological Specimen Banks; Health Facilities; Health Care Facilities Workforce and Services

Central Study Contacts

Sheng Liu, Doctor

CONTACT

13622284795; liush87@mail.sysu.edu.cn

Jing Su

CONTACT

15999937669; sujing@gzzoc.com

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 23, 2026
• First Posted: July 7, 2026
• Study Start: January 16, 2026
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: July 7, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)