Spatiotemporal transcriptomic atlas of mouse organogenesis using DNA nanoball-patterned arrays
Ao Chen, Sha Liao, Mengnan Cheng, Kailong Ma, Liang Wu, Yiwei Lai, Xiaojie Qiu, Jin Min Yang, Jiangshan Xu, Shijie Hao, Xin Wang, Huifang Lü, Xi Chen, Xing Liu, Xin Huang, Li Zhao, Hong Yan, Yujia Jiang, Jian Peng, Shuai Liu, Mengzhe Shen, Chuanyu Liu, Quanshui Li, Yue Yuan, Xiaoyu Wei, Huiwen Zheng, Weimin Feng, Zhifeng Wang, Yang Liu, Zhaohui Wang, Yunzhi Yang, Haitao Xiang, Lei Han, Baoming Qin, Peng-Cheng Guo, Guangyao Lai, Pura Muñoz‐Cánoves, Patrick H. Maxwell, Jean Paul Thiery, Qingfeng Wu, Fuxiang Zhao, Bichao Chen, Mei Li, Xi Dai, Shuai Wang, Haoyan Kuang, Junhou Hui, Liqun Wang, Ji‐Feng Fei, Ou Wang, Xiaofeng Wei, Haorong Lu, Bo Wang, Shiping Liu, Ying Gu, Ming Ni, Wenwei Zhang, Feng Mu, Ye Yin, Huanming Yang, Michael Lisby, Richard J. Cornall, Jan Mulder, Mathias Uhlén, Miguel A. Esteban, Yuxiang Li, Longqi Liu, Xun Xu, Jian Wang
Abstract
Spatially resolved transcriptomic technologies are promising tools to study complex biological processes such as mammalian embryogenesis. However, the imbalance between resolution, gene capture, and field of view of current methodologies precludes their systematic application to analyze relatively large and three-dimensional mid- and late-gestation embryos. Here, we combined DNA nanoball (DNB)-patterned arrays and in situ RNA capture to create spatial enhanced resolution omics-sequencing (Stereo-seq). We applied Stereo-seq to generate the mouse organogenesis spatiotemporal transcriptomic atlas (MOSTA), which maps with single-cell resolution and high sensitivity the kinetics and directionality of transcriptional variation during mouse organogenesis. We used this information to gain insight into the molecular basis of spatial cell heterogeneity and cell fate specification in developing tissues such as the dorsal midbrain. Our panoramic atlas will facilitate in-depth investigation of longstanding questions concerning normal and abnormal mammalian development.