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.
調査の概要
研究の種類
入学 (推定)
連絡先と場所
研究連絡先
- 名前：Sheng Liu, Doctor
- 電話番号：13622284795
- メール：liush87@mail.sysu.edu.cn
研究連絡先のバックアップ
- 名前：Jing Su
- 電話番号：15999937669
- メール：sujing@gzzoc.com
研究場所
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Guangdong
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Guangzhou、Guangdong、中国、510060
- 募集
- Zhongshan Ophthalmic Center, Sun Yat-sen University
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コンタクト：
- Sheng Liu
- 電話番号：13622284795
- メール：liush87@mail.sysu.edu.cn
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主任研究者：
- Sheng Liu
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参加基準
適格基準
就学可能な年齢
- 子
- 大人
- 高齢者
健康ボランティアの受け入れ
サンプリング方法
調査対象母集団
説明
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.
研究計画
研究はどのように設計されていますか？
デザインの詳細
コホートと介入
グループ/コホート |
介入・治療 |
|---|---|
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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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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Single-cell transcriptomic atlas and developmental trajectory of embryonic retinal and visual cortical neurons
時間枠：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
時間枠：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
時間枠：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
時間枠：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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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Action potential firing patterns of embryonic visual neurons
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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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協力者と研究者
出版物と役立つリンク
一般刊行物
- 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.
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
キーワード
追加の関連 MeSH 用語
その他の研究ID番号
- IIT2025136
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IPD プランの説明
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