Single-cell spatial reconstruction reveals global division of labour in the mammalian liver.
Single-cell spatial reconstruction reveals global division of labour in the mammalian liver.
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DOI：
10.1038/nature21065
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发表时间：
2017-02-16
期刊：
影响因子：
64.8
通讯作者：
Itzkovitz S
中科院分区：
文献类型：
--
作者：
Halpern KB;Shenhav R;Matcovitch-Natan O;Toth B;Lemze D;Golan M;Massasa EE;Baydatch S;Landen S;Moor AE;Brandis A;Giladi A;Avihail AS;David E;Amit I;Itzkovitz S
哺乳动物肝脏由六边形小叶组成，这些小叶被血流和形态发生素径向极化。关键的肝脏基因已被证明是差异表达的沿着小叶轴，一种现象称为zonation，但详细的全基因组重建的这种空间分工尚未实现。在这里，我们测量了成千上万的小鼠肝细胞的整个转录组，并推断其小叶坐标的基础上的一组分区的地标基因，其特征在于与单分子荧光原位杂交。使用这种方法，我们获得了高空间分辨率的所有肝脏基因的分区配置文件。我们发现，大约50%的肝脏基因是显着的分区，并揭示了丰富的非单调的配置文件，峰值在中间小叶层。这些包括胆汁酸生物合成酶的空间顺序，其与它们在酶级联中的位置相匹配。我们的方法可以促进其他哺乳动物器官的类似空间基因组蓝图的重建。
The mammalian liver consists of hexagon-shaped lobules that are radially polarized by blood flow and morphogens,,,. Key liver genes have been shown to be differentially expressed along the lobule axis, a phenomenon termed zonation,, but a detailed genome-wide reconstruction of this spatial division of labour has not been achieved. Here we measure the entire transcriptome of thousands of mouse liver cells and infer their lobule coordinates on the basis of a panel of zonated landmark genes, characterized with single-molecule fluorescencein situhybridization. Using this approach, we obtain the zonation profiles of all liver genes with high spatial resolution. We find that around 50% of liver genes are significantly zonated and uncover abundant non-monotonic profiles that peak at the mid-lobule layers. These include a spatial order of bile acid biosynthesis enzymes that matches their position in the enzymatic cascade. Our approach can facilitate the reconstruction of similar spatial genomic blueprints for other mammalian organs.