Spatiotemporal transcriptomic atlas of mouse organogenesis using DNA nanoball-patterned arrays

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 l...

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Published in:Cell 2022-05, Vol.185 (10), p.1777-1792.e21
Main Authors: Chen, Ao, Liao, Sha, Cheng, Mengnan, Ma, Kailong, Wu, Liang, Lai, Yiwei, Qiu, Xiaojie, Yang, Jin, Xu, Jiangshan, Hao, Shijie, Wang, Xin, Lu, Huifang, Chen, Xi, Liu, Xing, Huang, Xin, Li, Zhao, Hong, Yan, Jiang, Yujia, Peng, Jian, Liu, Shuai, Shen, Mengzhe, Liu, Chuanyu, Li, Quanshui, Yuan, Yue, Wei, Xiaoyu, Zheng, Huiwen, Feng, Weimin, Wang, Zhifeng, Liu, Yang, Wang, Zhaohui, Yang, Yunzhi, Xiang, Haitao, Han, Lei, Qin, Baoming, Guo, Pengcheng, Lai, Guangyao, Muñoz-Cánoves, Pura, Maxwell, Patrick H., Thiery, Jean Paul, Wu, Qing-Feng, Zhao, Fuxiang, Chen, Bichao, Li, Mei, Dai, Xi, Wang, Shuai, Kuang, Haoyan, Hui, Junhou, Wang, Liqun, Fei, Ji-Feng, Wang, Ou, Wei, Xiaofeng, Lu, Haorong, Wang, Bo, Liu, Shiping, Gu, Ying, Ni, Ming, Zhang, Wenwei, Mu, Feng, Yin, Ye, Yang, Huanming, Lisby, Michael, Cornall, Richard J., Mulder, Jan, Uhlén, Mathias, Esteban, Miguel A., Li, Yuxiang, Liu, Longqi, Xu, Xun, Wang, Jian
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Language:eng
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Summary: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. [Display omitted] •Stereo-seq enables large field-of-view spatial transcriptomics at cellular resolution•Stereo-seq reveals the spatial cell-type heterogeneity of mouse embryonic tissues•Stereo-seq maps the spatiotemporal transcriptomic dynamics during mouse organogenesis•Stereo-seq defines the spatiotemporal window of developmental disease vulnerability Stereo-seq combines DNA nanoball-patterned arrays and tissue RNA capture to achieve large field-of-view spatial transcriptomics at cellular resolution, enabling the dissection of spatial cell-type heterogeneity of mouse embryonic tissues.
ISSN:0092-8674
1097-4172
1097-4172