Continuum of Gene-Expression Profiles Provides Spatial Division of Labor within a Differentiated Cell Type
Continuum of Gene-Expression Profiles Provides Spatial Division of Labor within a Differentiated Cell Type
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DOI：
10.1016/j.cels.2018.12.008
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发表时间：
2019-01-23
期刊：
影响因子：
9.3
通讯作者：
Alon, Uri
中科院分区：
文献类型：
--
作者：
Adler, Miri;Kohanim, Yael Korem;Alon, Uri
单细胞基因表达揭示了分化细胞类型内的多样性。通常，相同类型的细胞显示出连续的基因表达模式。这种连续基因表达模式的起源尚不清楚。为了解决这个问题，我们开发了一个理论来理解连续体如何在细胞共同参与几项任务的组织中提供劳动分工。我们发现，当组织中存在影响每个任务性能的空间梯度时，连续体是最佳的。该连续体被限制在一个多面体内，该多面体的顶点是每个任务的最佳表达轮廓。我们使用肠绒毛和肝细胞的单细胞基因表达来测试这一点，肠绒毛和肝细胞分别在基因表达空间中形成弯曲的1D轨迹和完整的3D四面体。我们推断这两种类型的细胞的任务和特征的任务专家细胞的空间分区。这种方法通常可以应用于其他组织。
Single-cell gene expression reveals the diversity within a differentiated cell type. Often, cells of the same type show a continuum of gene-expression patterns. The origin of such continuum gene-expression patterns is unclear. To address this, we develop a theory to understand how a continuumprovides division of labor in a tissue in which cells collectively contribute to several tasks. We find that a continuum is optimal when there are spatial gradients in the tissue that affect the performance in each task. The continuum is bounded inside a polyhedron whose vertices are expression profiles optimal at each task. We test this using single-cell gene expression for intestinal villi and liver hepatocytes, which form a curved 1D trajectory and a full 3D tetrahedron in gene-expression space, respectively. We infer the tasks for both cell types and characterize the spatial zonation of the task-specialist cells. This approach can be generally applied to other tissues.