使用DNA纳米球图案化阵列构建的小鼠器官发生时空转录组图谱。

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

作者信息

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

机构信息

BGI-Shenzhen, Shenzhen 518103, China; Department of Biology, University of Copenhagen, Copenhagen 2200, Denmark.

BGI-Shenzhen, Shenzhen 518103, China.

出版信息

Cell. 2022 May 12;185(10):1777-1792.e21. doi: 10.1016/j.cell.2022.04.003. Epub 2022 May 4.

DOI:10.1016/j.cell.2022.04.003

PMID:35512705

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.

摘要

空间分辨转录组技术是研究复杂生物过程（如哺乳动物胚胎发生）的有前景的工具。然而，当前方法在分辨率、基因捕获和视野之间的不平衡阻碍了它们系统地应用于分析相对较大的三维中晚期妊娠胚胎。在这里，我们结合了DNA纳米球（DNB）图案化阵列和原位RNA捕获技术，创建了空间增强分辨率组学测序（Stereo-seq）。我们应用Stereo-seq生成了小鼠器官发生时空转录组图谱（MOSTA），该图谱以单细胞分辨率和高灵敏度绘制了小鼠器官发生过程中转录变化的动力学和方向性。我们利用这些信息深入了解发育组织（如背侧中脑）中空间细胞异质性和细胞命运特化的分子基础。我们的全景图谱将有助于深入研究有关正常和异常哺乳动物发育的长期问题。