Spatiotemporal transcriptomic atlas of mouse organogenesis using DNA nanoball patterned arrays
Author:
Chen Ao, Liao Sha, Cheng Mengnan, Ma Kailong, Wu Liang, Lai Yiwei, Qiu Xiaojie, Yang Jin, Li Wenjiao, Xu Jiangshan, Hao ShijieORCID, Wang Xin, Lu Huifang, Chen Xi, Liu Xing, Huang Xin, Lin Feng, Li Zhao, Hong Yan, Fu Defeng, Jiang Yujia, Peng Jian, Liu Shuai, Shen Mengzhe, Liu Chuanyu, Li Quanshui, Yuan Yue, Zheng Huiwen, Wang Zhifeng, Wang Zhaohui, Huang Xin, Xiang Haitao, Han Lei, Qin Baoming, Guo Pengcheng, Cánoves Pura Muñoz-, Thiery Jean Paul, Wu QingfengORCID, Zhao Fuxiang, Li Mei, Kuang Haoyan, Hui Junhou, Wang Ou, Lu Haorong, Wang Bo, Liu Shiping, Ni Ming, Zhang Wenwei, Mu Feng, Yin Ye, Yang Huanming, Lisby Michael, Cornall Richard J., Mulder Jan, Uhlen Mathias, Esteban Miguel A., Li Yuxiang, Liu Longqi, Xu Xun, Wang Jian
Abstract
SUMMARYSpatially resolved transcriptomic technologies are promising tools to study cell fate decisions in a physical microenvironment, which is fundamental for enhancing our knowledge of mammalian development. However, the imbalance between resolution, transcript capture and field of view of current methodologies precludes their systematic application to analyze relatively large and three-dimensional mid- and late-gestation mammalian embryos. Here, we combined DNA nanoball (DNB) patterned arrays and tissue RNA capture to create SpaTial Enhanced REsolution Omics-sequencing (Stereo-seq). This approach allows transcriptomic profiling of large histological sections with high resolution and sensitivity. We have applied Stereo-seq to study the kinetics and directionality of transcriptional variation in a time course of mouse organogenesis. We used this information to gain insight into the molecular basis of regional specification, neuronal migration and differentiation in the developing brain. Furthermore, we mapped the expression of a panel of developmental disease-related loci on our global transcriptomic maps to define the spatiotemporal windows of tissue vulnerability. Our panoramic atlas constitutes an essential resource to investigate longstanding questions concerning normal and abnormal mammalian development.
Publisher
Cold Spring Harbor Laboratory
Cited by
42 articles.
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