一份果蝇单细胞3D时空多组学图谱揭示了细胞类型分化的全景关键调节因子。

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

作者信息

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

机构信息

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.

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.

出版信息

Cell. 2025 Jun 24. doi: 10.1016/j.cell.2025.05.047.

DOI:10.1016/j.cell.2025.05.047

PMID:40578340

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.

摘要

多细胞生物的发育是一个高度复杂的过程，受到众多基因和信号通路在空间和时间上的严格调控。在此，我们展示了Flysta3D-v2，这是一个涵盖模式生物果蝇从胚胎到蛹整个发育生命周期的综合多组学图谱。我们的数据集包含3D单细胞空间转录组学、单细胞转录组学和单细胞染色质可及性信息。通过整合多模态数据，我们生成了整个生物体在计算机模拟中的发育连续3D模型。我们进一步构建了组织发育轨迹，揭示了细胞类型分化的详细情况。以中肠为重点，我们鉴定了参与中肠细胞类型调控的转录因子，并验证了exex是铜细胞发育的关键调节因子。这个广泛的图谱提供了丰富的资源，并作为一个系统平台，用于在超高时空分辨率下利用整合的单细胞数据研究果蝇的发育。