德国马克斯·普朗克分子遗传学研究所Alexander Meissner课题组在研究中取得进展。他们揭示了器官初始发育时小鼠胚胎的时空转录组图谱。相关论文于2023年7月6日发表于国际学术期刊《自然—遗传学》杂志。

研究人员使用Slide-seq构建了完整胚胎8.5天（E）和E9.0以及部分E9.5胚胎的空间转录组图。为了支持它们的效用，研究人员研发了sc3D，这是一种用于重建和探索三维“虚拟胚胎”的工具，可对区域化的基因表达模式进行定量研究。研究人员对发育过程中神经管发育的主要胚胎轴进行了测量，并揭示了几个以前未知的具有不同空间模式的基因。研究还发现了Tbx6突变胚胎中出现的与“异位”神经管相互矛盾的转录身份。综上所述，该研究提出了可用于对整个胚胎结构和突变表型进行时空研究的实验和计算模型。

据悉，基因表达的时空调控是胚胎正常发育所必需的。单细胞技术的使用改进了早期调控动力学的分辨率，包括小鼠胚胎发生过程中大多数细胞状态的详细分子模式。

附：英文原文

Title: Spatiotemporal transcriptomic maps of whole mouse embryos at the onset of organogenesis

Author: Sampath Kumar, Abhishek, Tian, Luyi, Bolondi, Adriano, Hernndez, Amlia Aragons, Stickels, Robert, Kretzmer, Helene, Murray, Evan, Wittler, Lars, Walther, Maria, Barakat, Gabriel, Haut, Leah, Elkabetz, Yechiel, Macosko, Evan Z., Guignard, Lo, Chen, Fei, Meissner, Alexander

Issue&Volume: 2023-07-06

Abstract: Spatiotemporal orchestration of gene expression is required for proper embryonic development. The use of single-cell technologies has begun to provide improved resolution of early regulatory dynamics, including detailed molecular definitions of most cell states during mouse embryogenesis. Here we used Slide-seq to build spatial transcriptomic maps of complete embryonic day (E) 8.5 and E9.0, and partial E9.5 embryos. To support their utility, we developed sc3D, a tool for reconstructing and exploring three-dimensional ‘virtual embryos’, which enables the quantitative investigation of regionalized gene expression patterns. Our measurements along the main embryonic axes of the developing neural tube revealed several previously unannotated genes with distinct spatial patterns. We also characterized the conflicting transcriptional identity of ‘ectopic’ neural tubes that emerge in Tbx6 mutant embryos. Taken together, we present an experimental and computational framework for the spatiotemporal investigation of whole embryonic structures and mutant phenotypes.

DOI: 10.1038/s41588-023-01435-6

Source: https://www.nature.com/articles/s41588-023-01435-6