Citations 2
An Integrated muti-omics cell atlas of the human trabecular meshwork and ciliary body
Jian, Jinjing , Bao, Xuan , Zheng, Y , Shao, Jianming , Yang, Tingting , Yaman, Ismail, Li, Jean , Chen, Han, Tolman, Nicholas, Sheridan, Carl, Zode, Gulab S., John, Simon W. M. , Stout, J Timothy, Stamer, Dan, Li, Yumei, Li, Jin , Shao, Jianming , Liu, Yutao , John, Simon Wm , Chen, Rui , Wang, Yi-Xiang , Tolman, Nicholas G. , Scheuermann, Richard H. , Zheng, Jie , Sheridan, Carl , Liu, Yutao , Du, Yiqin , Balasubramanian, Revathi , Zode, Gulab , Stout, J. Timothy, Li, Yumei
No container title available | June 23, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available
Abstract The trabecular meshwork (TM) and ciliary body (CB) regulate aqueous humor dynamics and intraocular pressure (IOP), and TM/Schlemm’s canal (SC) dysfunction underlies glaucoma. Here, we present a spatially resolved multi-omics atlas of human TM and CB, integrating snRNA-seq, scRNA-seq, and snATAC-seq from over one million cells and nuclei across 112 donors with Xenium spatial transcriptomics. We identified 9 major cell classes and 21 cell types, revealing heterogeneity, including undercharacterized fibroblast and epithelial subpopulations. Spatial mapping supported TM fibroblast zonation and CB epithelial organization. Regulatory analyses identified cell type–specific programs, including OTX/PAX networks in CB epithelium and SMAD3/TGF-β signaling in fibroblasts. Integration with glaucoma loci showed enrichment of non-coding variants in regulatory elements associated with POAG and PACG. Age- and ancestry-associated remodeling revealed divergent fibroblast aging with increased PIEZO1 , suggesting impaired outflow and elevated IOP. Together, this high-resolution atlas links cellular, regulatory, and genetic variation to anterior segment function and glaucoma susceptibility.
Integrative Multi-Omics Analysis Identifies a Functional Enhancer Driving Tumorigenesis in Head and Neck Squamous Cell Carcinoma
Liu, Xiaorong, Pu, Jane Jingya, Lu, Xiaoling , Wang, Evelyn Yilin, Jiang, Qianhui , Yu, Dan , Yan, Bin, Zhong, Qi, Yang, Ping, Su, Yu-Xiong, Yu, Dan , Xu, Pengfei , Lee, Victor , Song, Jinlin , Tran, Nhan L. , Guan, Xinyuan , Wang, Yi-Xiang
No container title available | February 5, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available
Abstract Enhancer is a critical epigenetic feature in head and neck squamous cell carcinoma (HNSCC), yet the functional roles of individual enhancers remain poorly understood. Here, we conducted an integrative multi-omics analysis based on publicly available ATAC-seq, H3K27ac ChIP-seq, transcriptomic profiling, and genetic association datasets to systematically map HNSCC-associated enhancers and their target genes. Integrating ATAC-seq and H3K27ac ChIP-seq, we identified 20,362 enhancers and 18,040 enhancer-associated genes, highlighting widespread regulatory complexity. Functional characterization of the TERT -associated enhancer GH05J001312 (GRCh38/hg38: chr5:1312099-1317743) revealed strong transcriptional activity in HNSCC. CRISPR-mediated deletion of a core sequence significantly reduced TERT expression, impaired cellular proliferation in vitro , and suppressed tumor growth in vivo , confirming its role as a key cis-regulatory element. RNA-seq analysis of enhancer-edited cells uncovered 742 differentially expressed genes enriched in cancer-related pathways, including MAPK and IL-17 signaling, indicating a broad transcriptional impact. Collectively, our findings establish GH05J001312 as a functional enhancer driving oncogenic programs in HNSCC and suggest enhancer-targeted strategies as a potential therapeutic avenue.