Stereo-cell: Spatial enhanced-resolution single-cell sequencing with high-density DNA nanoball-patterned arrays

Science. 2025 Aug 21;389(6762):eadr0475. doi: 10.1126/science.adr0475.

Sha Liao ^# ¹ ² ³, Xiaoxi Zhou ^# ¹, Chuanyu Liu ^# ¹ ⁴ ⁵ ⁶ ⁷, Chang Liu ^# ¹ ⁵ ⁶, Shijie Hao ^# ⁸ ⁹ ¹⁰, Hongyu Luo ^# ¹, Huan Hou ¹, Qian Liu ¹, Zhe Zhang ¹, Liyun Xiao ¹, Yuan Xu ³, Yaling Huang ² ¹¹ ¹², Sining Zhou ⁸ ⁹, Xuerong Li ⁸ ⁹, Yang Wang ² ¹³, Lulin Xie ², Zhichun Zhou ², Shichen Dong ², Yiru Wang ² ¹⁴, Xiaojing Xu ⁸ ⁹ ¹⁰, Pengcheng Guo ⁸ ⁹ ¹⁰, Xiumei Lin ⁸ ⁹, Jiajie Lei ² ¹⁵, Qiaoling Wang ², Yuxin Gong ⁴ ¹⁶, Jiaming Cheng ⁴, Zixin Yuan ⁴, Yongqing Yang ⁴ ¹³, Zhi Huang ⁴ ¹⁰, Shenglong Li ⁴ ¹⁰, Yuhui Zheng ² ¹³, Shichen Yang ² ¹³, Xin Huang ¹ ¹³, Weiqing Liu ², Mei Li ², Zhonghan Deng ², Xinyu Yang ⁴ ¹³, Jianhua Yin ¹ ⁵ ⁶, Yingjie Luo ¹ ⁵, Yiwei Lai ¹ ⁵ ⁶, Yue Yuan ¹ ⁴, Mengnan Cheng ¹ ⁴, Bo Wang ¹ ¹⁷ ¹⁸, Jiansong Ji ¹⁹, Miguel A Esteban ² ²⁰, Yuxiang Li ² ²¹, Ying Gu ¹ ²⁰, Yijun Ruan ²², Liang Chen ⁸ ⁹, Xiangdong Wang ⁷ ²³, Jun Xie ⁶ ²⁴, Jian Wang ² ²⁵, Longqi Liu ² ⁶ ⁸ ⁹ ¹³, Ao Chen ² ³ ¹², Xun Xu ¹ ⁶ ¹³ ²⁶

Affiliations

1 State Key Laboratory of Genome and Multi-omics Technologies, BGI Research, Shenzhen, China.
2 BGI Research, Shenzhen, China.
3 BGI Research, Chongqing, China.
4 BGI Research, Hangzhou, China.
5 Shenzhen Proof-of-Concept Center of Digital Cytopathology, BGI Research, Shenzhen, China.
6 Shanxi Medical University-BGI Collaborative Center for Future Medicine, Shanxi Medical University, Taiyuan, China.
7 Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, China.
8 State Key Laboratory of Genome and Multi-omics Technologies, BGI Research, Hangzhou, China.
9 Key Laboratory of Spatial Omics of Zhejiang Province, BGI Research, Hangzhou, China.
10 School of Biology and Biological Engineering, South China University of Technology, Guangzhou, China.
11 Department of Surgery, The Chinese University of Hong Kong, Shatin, Hong Kong Special Administrative Region, China.
12 Shenzhen Key Laboratory of Single-Cell Omics, BGI Research, Shenzhen, China.
13 College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China.
14 College of Life Sciences, South-Central Minzu University, Wuhan, China.
15 State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, China.
16 College of Life Science and Technology, Huazhong Agricultural University, Wuhan, China.
17 China National GeneBank, BGI Research, Shenzhen, China.
18 Shenzhen Key Laboratory of Environmental Microbial Genomics and Application, BGI Research, Shenzhen, China.
19 Zhejiang Key Laboratory of Imaging and Interventional Medicine, Department of Radiology, Lishui Central Hospital, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, China.
20 3DCStar lab, BGI, Shenzhen, China.
21 BGI Research, Wuhan, China.
22 Life Sciences Institute, Zhejiang University, Hangzhou, China.
23 Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.
24 MOE Key Laboratory of Coal Environmental Pathogenicity and Prevention, Shanxi Medical University, Taiyuan, China.
25 James D. Watson Institute of Genome Sciences, Hangzhou, China.
26 Guangdong Provincial Key Laboratory of Genome Read and Write, BGI Research, Shenzhen, China.
# Contributed equally.

PMID: 40839715 DOI: 10.1126/science.adr0475

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.

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