小柯机器人

英国剑桥大学J. C. Marioni等研究人员合作利用空间和单细胞转录组数据揭示小鼠的器官发育过程。相关论文于2021年9月6日在线发表于国际学术期刊《自然—生物技术》。

研究人员应用基于图像的单细胞转录组学方法——顺序荧光原位杂交（seqFISH），在小鼠胚胎8-12体节阶段的组织切片中检测387个目标基因的mRNA。通过将空间背景和多路转录测量与两个单细胞转录组图谱相结合，研究人员描述了整个胚胎的细胞类型，并证明了空间分辨率的基因表达可以通过seqFISH分析进行归纳。

研究人员使用这种高分辨率的空间图谱来描述了中脑-后脑边界（MHB）分化和发育中肠管的基本步骤。研究人员发现了单细胞RNA测序（scRNA-seq）数据中不明显的细胞分化轴，例如在肠管中食道和气管祖细胞群的早期背腹分离。这个方法为研究复杂组织和发育中的细胞命运决定提供了一种方法。

据介绍，单个细胞的分子分析推进了人们对发育分子基础的认识。然而，目前的方法大多依赖于将细胞从组织中分离出来，从而失去了调节过程的关键空间背景。

附：英文原文

Title: Integration of spatial and single-cell transcriptomic data elucidates mouse organogenesis

Author: Lohoff, T., Ghazanfar, S., Missarova, A., Koulena, N., Pierson, N., Griffiths, J. A., Bardot, E. S., Eng, C.-H. L., Tyser, R. C. V., Argelaguet, R., Guibentif, C., Srinivas, S., Briscoe, J., Simons, B. D., Hadjantonakis, A.-K., Gttgens, B., Reik, W., Nichols, J., Cai, L., Marioni, J. C.

Issue&Volume: 2021-09-06

Abstract: Molecular profiling of single cells has advanced our knowledge of the molecular basis of development. However, current approaches mostly rely on dissociating cells from tissues, thereby losing the crucial spatial context of regulatory processes. Here, we apply an image-based single-cell transcriptomics method, sequential fluorescence in situ hybridization (seqFISH), to detect mRNAs for 387 target genes in tissue sections of mouse embryos at the 8–12 somite stage. By integrating spatial context and multiplexed transcriptional measurements with two single-cell transcriptome atlases, we characterize cell types across the embryo and demonstrate that spatially resolved expression of genes not profiled by seqFISH can be imputed. We use this high-resolution spatial map to characterize fundamental steps in the patterning of the midbrain–hindbrain boundary (MHB) and the developing gut tube. We uncover axes of cell differentiation that are not apparent from single-cell RNA-sequencing (scRNA-seq) data, such as early dorsal–ventral separation of esophageal and tracheal progenitor populations in the gut tube. Our method provides an approach for studying cell fate decisions in complex tissues and development.

DOI: 10.1038/s41587-021-01006-2

Source: https://www.nature.com/articles/s41587-021-01006-2

Nature Biotechnology：《自然—生物技术》，创刊于1996年。隶属于施普林格·自然出版集团，最新IF：68.164
官方网址：https://www.nature.com/nbt/
投稿链接：https://mts-nbt.nature.com/cgi-bin/main.plex