A Drosophila single-cell 3D spatiotemporal multi-omics atlas unveils panoramic key regulators of cell-type differentiation

Mingyue Wang; Qinan Hu; Zhencheng Tu; Lingshi Kong; Tengxiang Yu; Zihan Jia; Yuetian Wang; Jiajun Yao; Rong Xiang; Zhan Chen; Yan Zhao; Yanfei Zhou; Qing Ye; Kang Ouyang; Xianzhe Wang; Yinqi Bai; Zhenyu Yang; Hanxiang Wang; Yanru Wang; Hanxiang Jiang; Tao Yang; Jing Chen; Yunting Huang; Ni Yin; Wenyuan Mo; Wenfu Liang; Chang Liu; Xiumei Lin; Chuanyu Liu; Ying Gu; Wei Chen; Longqi Liu; Xun Xu; Yuhui Hu

doi:10.1016/j.cell.2025.05.047

A Drosophila single-cell 3D spatiotemporal multi-omics atlas unveils panoramic key regulators of cell-type differentiation

Cell. 2025 Jun 24:S0092-8674(25)00629-4. doi: 10.1016/j.cell.2025.05.047. Online ahead of print.

Authors

Mingyue Wang¹, Qinan Hu², Zhencheng Tu³, Lingshi Kong⁴, Tengxiang Yu⁴, Zihan Jia³, Yuetian Wang⁴, Jiajun Yao⁵, Rong Xiang³, Zhan Chen³, Yan Zhao⁶, Yanfei Zhou⁴, Qing Ye⁷, Kang Ouyang³, Xianzhe Wang⁷, Yinqi Bai⁷, Zhenyu Yang⁴, Hanxiang Wang⁴, Yanru Wang⁴, Hanxiang Jiang⁴, Tao Yang⁸, Jing Chen⁸, Yunting Huang⁸, Ni Yin⁸, Wenyuan Mo⁸, Wenfu Liang⁸, Chang Liu⁷, Xiumei Lin⁷, Chuanyu Liu⁹, Ying Gu⁹, Wei Chen¹⁰, Longqi Liu¹¹, Xun Xu¹², Yuhui Hu¹³

Affiliations

¹ BGI Research, Hangzhou 310030, China; State Key Laboratory of Genome and Multi-omics Technologies, BGI Research, Hangzhou 310030, China; School of Computer Science and Technology, Zhejiang University of Science and Technology, Hangzhou 310023, China; Department of Systems Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen 518055, China.
² Department of Pharmacology, School of Medicine, Southern University of Science and Technology, Shenzhen 518055, China; Joint Laboratory of Guangdong-Hong Kong Universities for Vascular Homeostasis and Diseases, School of Medicine, Southern University of Science and Technology, Shenzhen 518055, Guangdong, China; Shenzhen Key Laboratory of Gene Regulation and Systems Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen 518055, China. Electronic address: huqn@sustech.edu.cn.
³ BGI Research, Hangzhou 310030, China; College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China.
⁴ Department of Pharmacology, School of Medicine, Southern University of Science and Technology, Shenzhen 518055, China; Joint Laboratory of Guangdong-Hong Kong Universities for Vascular Homeostasis and Diseases, School of Medicine, Southern University of Science and Technology, Shenzhen 518055, Guangdong, China; Shenzhen Key Laboratory of Gene Regulation and Systems Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen 518055, China.
⁵ School of Ecology and Environment, Northwestern Polytechnical University, Xi'an 710072, China.
⁶ Department of Pharmacology, School of Medicine, Southern University of Science and Technology, Shenzhen 518055, China; Joint Laboratory of Guangdong-Hong Kong Universities for Vascular Homeostasis and Diseases, School of Medicine, Southern University of Science and Technology, Shenzhen 518055, Guangdong, China; Department of Computational Molecular Biology, Max Planck Institute for Molecular Genetics, Ihnestraße 63-73, Berlin 14195, Germany.
⁷ BGI Research, Hangzhou 310030, China.
⁸ China National GeneBank, BGI Research, Shenzhen 518083, China.
⁹ BGI Research, Hangzhou 310030, China; BGI Research, Shenzhen 518083, China.
¹⁰ Department of Systems Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen 518055, China; Shenzhen Key Laboratory of Gene Regulation and Systems Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen 518055, China.
¹¹ BGI Research, Hangzhou 310030, China; State Key Laboratory of Genome and Multi-omics Technologies, BGI Research, Hangzhou 310030, China; School of Computer Science and Technology, Zhejiang University of Science and Technology, Hangzhou 310023, China. Electronic address: liulongqi@genomics.cn.
¹² BGI Research, Hangzhou 310030, China; State Key Laboratory of Genome and Multi-omics Technologies, BGI Research, Hangzhou 310030, China. Electronic address: xuxun@genomics.cn.
¹³ Department of Pharmacology, School of Medicine, Southern University of Science and Technology, Shenzhen 518055, China; Joint Laboratory of Guangdong-Hong Kong Universities for Vascular Homeostasis and Diseases, School of Medicine, Southern University of Science and Technology, Shenzhen 518055, Guangdong, China; Shenzhen Key Laboratory of Gene Regulation and Systems Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen 518055, China; Research Center for Chemical Biology and Omics Analysis, Guangming Advanced Research Institute, Southern University of Science and Technology, Shenzhen 518055, China; SUSTech Homeostatic Medicine Institute, School of Medicine, Southern University of Science and Technology, Shenzhen 518055, China. Electronic address: huyh@sustech.edu.cn.

PMID: 40578340
DOI: 10.1016/j.cell.2025.05.047

Abstract

The development of a multicellular organism is a highly intricate process tightly regulated by numerous genes and pathways in both spatial and temporal manners. Here, we present Flysta3D-v2, a comprehensive multi-omics atlas of the model organism Drosophila spanning its developmental lifespan from embryo to pupa. Our datasets encompass 3D single-cell spatial transcriptomic, single-cell transcriptomic, and single-cell chromatin accessibility information. Through the integration of multimodal data, we generated developmentally continuous in silico 3D models of the entire organism. We further constructed tissue development trajectories that uncover the detailed profiles of cell-type differentiation. With a focus on the midgut, we identified transcription factors involved in midgut cell-type regulation and validated exex as a key regulator of copper cell development. This extensive atlas provides a rich resource and serves as a systematic platform for studying Drosophila development with integrated single-cell data at ultra-high spatiotemporal resolution.

Keywords: 3D developmental model; Drosophila development; Drosophila exex; Flysta3D; single-cell multi-omics; spatial transcriptomics.