Mapping of the Developmental Atlas of the Visual System and Research on Embryonic Neurogenesis Phenomena
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.
연구 개요
연구 유형
등록 (추정된)
연락처 및 위치
연구 연락처
- 이름: Sheng Liu, Doctor
- 전화번호: 13622284795
- 이메일: liush87@mail.sysu.edu.cn
연구 연락처 백업
- 이름: Jing Su
- 전화번호: 15999937669
- 이메일: sujing@gzzoc.com
연구 장소
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Guangdong
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Guangzhou, Guangdong, 중국, 510060
- 모병
- Zhongshan Ophthalmic Center, Sun Yat-sen University
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연락하다:
- Sheng Liu
- 전화번호: 13622284795
- 이메일: liush87@mail.sysu.edu.cn
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수석 연구원:
- Sheng Liu
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참여기준
자격 기준
공부할 수 있는 나이
- 어린이
- 성인
- 고령자
건강한 자원 봉사자를 받아들입니다
샘플링 방법
연구 인구
설명
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
코호트 및 개입
그룹/코호트 |
개입 / 치료 |
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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.
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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.
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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.
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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.
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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Single-cell transcriptomic atlas and developmental trajectory of embryonic retinal and visual cortical neurons
기간: Day 1 of tissue collection
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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.
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Day 1 of tissue collection
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Genome-wide chromatin open regions in embryonic visual tissues
기간: Day 1 of tissue collection
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Genome-wide chromatin open regions are detected via snATAC-seq on embryonic ocular and brain tissues from case and control groups.
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Day 1 of tissue collection
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Differential chromatin accessibility between normal and malformed embryonic visual tissues
기간: Day 1 of tissue collection
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Differential chromatin accessibility signals are identified via integrated analysis of snATAC-seq and scRNA-seq data from embryonic ocular and brain tissues.
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Day 1 of tissue collection
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Candidate pathogenic genes underlying embryonic visual developmental abnormalities
기간: Day 1 of tissue collection
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Genes linked to abnormal embryonic visual development are screened based on differential chromatin and transcriptomic profiles.
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Day 1 of tissue collection
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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Action potential firing patterns of embryonic visual neurons
기간: Day 1 of tissue collection
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Action potential firing patterns are recorded via combined Patch-seq and MEA on primary cultured retinal and visual cortical neurons from case and control embryonic tissues.
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Day 1 of tissue collection
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Synchronous electrical activity of embryonic neuronal networks
기간: Day 1 of tissue collection
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Neuronal network synchronous electrical activity is recorded via combined Patch-seq and MEA on primary cultured retinal and visual cortical neurons from case and control embryonic tissues.
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Day 1 of tissue collection
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Spatial expression localization of key visual development genes detected by RNAscope
기간: The day 1 of embryonic tissue collection after clinical termination of pregnancy
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RNAscope in situ hybridization is conducted on embryonic retinal and brain tissue slices to visualize the spatial distribution and quantitative expression levels of candidate pathogenic genes screened from multi-omics data.
Compare the spatial gene expression differences between normal embryonic visual tissues and tissues with ocular developmental defects.
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The day 1 of embryonic tissue collection after clinical termination of pregnancy
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Differentially expressed proteins identified via global proteome sequencing
기간: Day 1 of tissue collection
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Global proteome sequencing is performed on embryonic ocular and brain tissues to generate lists of differentially expressed proteins linked to retinal neurogenesis and visual cortical development.
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Day 1 of tissue collection
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Spatial localization and expression abundance of proteins via immunohistochemistry
기간: Day 1 of tissue collection
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Immunohistochemistry staining is applied on embryonic tissue sections to detect spatial localization and expression abundance of core differentially expressed proteins.
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Day 1 of tissue collection
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공동 작업자 및 조사자
간행물 및 유용한 링크
일반 간행물
- 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.
- 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.
- 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.
- 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.
연구 기록 날짜
연구 주요 날짜
연구 시작 (실제)
기본 완료 (추정된)
연구 완료 (추정된)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (실제)
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
키워드
추가 관련 MeSH 약관
기타 연구 ID 번호
- IIT2025136
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
IPD 계획 설명
이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .