Li Jin, Wang Jun, Ibarra Ignacio L, Cheng Xuesen, Luecken Malte D, Lu Jiaxiong, Monavarfeshani Aboozar, Yan Wenjun, Zheng Yiqiao, Zuo Zhen, Colborn Samantha Lynn Zayas, Cortez Berenice Sarahi, Owen Leah A, Tran Nicholas M, Shekhar Karthik, Sanes Joshua R, Stout J Timothy, Chen Shiming, Li Yumei, DeAngelis Margaret M, Theis Fabian J, Chen Rui
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States.
Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, United States.
Res Sq. 2023 Nov 17:rs.3.rs-3471275. doi: 10.21203/rs.3.rs-3471275/v1.
Single-cell sequencing has revolutionized the scale and resolution of molecular profiling of tissues and organs. Here, we present an integrated multimodal reference atlas of the most accessible portion of the mammalian central nervous system, the retina. We compiled around 2.4 million cells from 55 donors, including 1.4 million unpublished data points, to create a comprehensive human retina cell atlas (HRCA) of transcriptome and chromatin accessibility, unveiling over 110 types. Engaging the retina community, we annotated each cluster, refined the Cell Ontology for the retina, identified distinct marker genes, and characterized cis-regulatory elements and gene regulatory networks (GRNs) for these cell types. Our analysis uncovered intriguing differences in transcriptome, chromatin, and GRNs across cell types. In addition, we modeled changes in gene expression and chromatin openness across gender and age. This integrated atlas also enabled the fine-mapping of GWAS and eQTL variants. Accessible through interactive browsers, this multimodal cross-donor and cross-lab HRCA, can facilitate a better understanding of retinal function and pathology.
单细胞测序彻底改变了组织和器官分子图谱的规模和分辨率。在此，我们展示了哺乳动物中枢神经系统最易获取部分——视网膜的一个整合多模态参考图谱。我们汇集了来自55名供体的约240万个细胞，包括140万个未发表的数据点，以创建一个涵盖转录组和染色质可及性的全面人类视网膜细胞图谱（HRCA），揭示了超过110种细胞类型。我们与视网膜研究领域的人员合作，对每个细胞簇进行注释，完善视网膜的细胞本体，鉴定出不同的标记基因，并表征这些细胞类型的顺式调控元件和基因调控网络（GRN）。我们的分析揭示了不同细胞类型在转录组、染色质和GRN方面的有趣差异。此外，我们模拟了不同性别和年龄的基因表达和染色质开放性变化。这个整合图谱还能够对全基因组关联研究（GWAS）和表达定量性状位点（eQTL）变体进行精细定位。通过交互式浏览器可访问的这个多模态跨供体和跨实验室的HRCA，有助于更好地理解视网膜功能和病理学。
