Spatiotemporal transcriptomic atlas of mouse organogenesis using DNA nanoball patterned arrays

转录组 计算生物学 生物 器官发生 计算机科学 细胞生物学 遗传学 基因表达 基因
作者
Ao Chen,Sha Liao,Mengnan Cheng,Kailong Ma,Liang Wu,Yiwei Lai,Xiaojie Qiu,Jin Min Yang,Wenjiao Li,Jiangshan Xu,Shijie Hao,Xin Wang,Huifang Lü,Xi Chen,Xing Liu,Xin Huang,Feng Lin,Li Zhao,Hong Yan,Defeng Fu,Yujia Jiang,Jian Peng,Shuai Liu,Mengzhe Shen,Chuanyu Liu,Quanshui Li,Yue Yuan,Huiwen Zheng,Zhifeng Wang,Zhaohui Wang,Xin Huang,Haitao Xiang,Lei Han,Baoming Qin,Peng-Cheng Guo,Pura Muñoz- Cánoves,Jean Paul Thiery,Qing-Feng Wu,Fuxiang Zhao,Mei Li,Haoyan Kuang,Junhou Hui,Ou Wang,Haorong Lu,Bo Wang,Shiping Liu,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
标识
DOI:10.1101/2021.01.17.427004
摘要

SUMMARY Spatially 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.
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