Stereo-cell: Spatial enhanced-resolution single-cell sequencing with high-density DNA nanoball-patterned arrays
Sha Liao, Xiaoxi Zhou, Chuanyu Liu, Chang Liu, Shijie Hao, Hongyu Luo, Huan Hou, Qian Liu, Zhe Zhang, Liyun Xiao, Yuan Xu, Yaling Huang, Sining Zhou, Xuerong Li, Yang Wang, Lulin Xie, Zhichun Zhou, Shichen Dong, Yiru Wang, Xiaojing Xu, Xiaojing Xu, P. Guo, Xiumei Lin, Jiajie Lei, Qiaoling Wang, Yuxin Gong, Jiaming Cheng, Zixin Yuan, Yongqing Yang, Zhi Rui Huang, Shenglong Li, Yuhui Zheng, Shichen Yang, Xin Huang, Weiqing Liu, Mei Li, Zhonghan Deng, Xinyu Yang, Jianhua Yin, Yingjie Luo, Yiwei Lai, Yue Yuan, Mengnan Cheng, Bo Wang, Jiansong Ji, Miguel A. Esteban, Yuxiang Li, Ying Gu, Yijun Ruan, Liang Chen, Xiangdong Wang, Jun Xie, Jian Wang, Longqi Liu, Ao Chen, Xun Xu, Xun Xu
Abstract
Single-cell sequencing technologies have advanced our understanding of cellular heterogeneity and biological complexity. However, existing methods face limitations in throughput, capture uniformity, cell size flexibility, and technical extensibility. We present Stereo-cell, a spatial enhanced-resolution single-cell sequencing platform based on high-density DNA nanoball (DNB)-patterned arrays, which enables scalable and unbiased cell capture at a wide input range and supports high-fidelity transcriptome profiling. Stereo-cell further allows integration with imaging-based modalities and multiomics strategies, including immunofluorescence and epitope profiling. This platform is also compatible with profiling extracellular vesicles, microstructures, and large cells, whereas its spatial resolution facilitates in situ analysis of cell-cell interactions, cellular microenvironments, and subcellular transcript localization. Together, Stereo-cell provides a flexible framework for expanding single-cell research applications.