Systems Biology of Gene Regulatory Elements, Berlin Institute for Medical Systems Biology (BIMSB), Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany.
Systems Biology of Neural Tissue Differentiation, BIMSB, MDC, 13125 Berlin, Germany.
Science. 2017 Oct 13;358(6360):194-199. doi: 10.1126/science.aan3235. Epub 2017 Aug 31.
By the onset of morphogenesis, embryos consist of about 6000 cells that express distinct gene combinations. Here, we used single-cell sequencing of precisely staged embryos and devised DistMap, a computational mapping strategy to reconstruct the embryo and to predict spatial gene expression approaching single-cell resolution. We produced a virtual embryo with about 8000 expressed genes per cell. Our interactive Virtual Expression eXplorer (DVEX) database generates three-dimensional virtual in situ hybridizations and computes gene expression gradients. We used DVEX to uncover patterned expression of transcription factors and long noncoding RNAs, as well as signaling pathway components. Spatial regulation of Hippo signaling during early embryogenesis suggests a mechanism for establishing asynchronous cell proliferation. Our approach is suitable to generate transcriptomic blueprints for other complex tissues.
胚胎在形态发生开始时由大约 6000 个细胞组成，这些细胞表达不同的基因组合。在这里，我们使用精确分期胚胎的单细胞测序，并设计了 DistMap，这是一种计算映射策略，用于重建胚胎并预测接近单细胞分辨率的空间基因表达。我们生成了一个具有大约 8000 个每个细胞表达基因的虚拟胚胎。我们的交互式虚拟表达 eXplorer（DVEX）数据库生成三维虚拟原位杂交并计算基因表达梯度。我们使用 DVEX 来揭示转录因子和长非编码 RNA 以及信号通路成分的图案表达。Hippo 信号在早期胚胎发生过程中的空间调节提示了建立异步细胞增殖的机制。我们的方法适用于为其他复杂组织生成转录组蓝图。
