Emergence of division of labor in tissues through cell interactions and spatial cues.
Emergence of division of labor in tissues through cell interactions and spatial cues.
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DOI：
10.1016/j.celrep.2023.112412
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发表时间：
2023-05-30
期刊：
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
多细胞生物中的大多数细胞类型可以执行多种功能。然而，并非所有功能都可以由相同的细胞同时最佳地执行。在单个细胞水平上不兼容的功能可以在细胞群水平上执行，其中细胞分工并专门从事不同的功能。分工可能是由于组织环境的指导或通过自组织而产生的。在这里，我们开发了一个计算框架来研究这些机制对细胞类型群体内的劳动分工的贡献。通过权衡下优化集体细胞任务表现，我们发现细胞间相互作用与指导信号可以产生可区分的表达模式。我们提出了一种在特殊细胞之间构建配体-受体网络的方法，并用它从单细胞 RNA 测序 (RNA-seq) 和基质细胞、上皮细胞和免疫细胞的空间转录组数据来推断分工机制。我们的框架可用于表征组织内细胞相互作用的复杂性。分工理论预测了不同的、依赖于机制的空间模式专门细胞的空间接近性表明细胞相互作用的参与原型串扰网络揭示了专门细胞之间的相互作用模式肠细胞和成纤维细胞例证了不同的分工策略可以驱动组织分工的两种机制是外部信号梯度和细胞-细胞相互作用。最佳任务分配理论解释了如何区分单细胞和空间组学数据中的两种策略。这已在结肠成纤维细胞、肠上皮细胞、肺成纤维细胞和巨噬细胞中得到证实。
Most cell types in multicellular organisms can perform multiple functions. However, not all functions can be optimally performed simultaneously by the same cells. Functions incompatible at the level of individual cells can be performed at the cell population level, where cells divide labor and specialize in different functions. Division of labor can arise due to instruction by tissue environment or through self-organization. Here, we develop a computational framework to investigate the contribution of these mechanisms to division of labor within a cell-type population. By optimizing collective cellular task performance under trade-offs, we find that distinguishable expression patterns can emerge from cell-cell interactions versus instructive signals. We propose a method to construct ligand-receptor networks between specialist cells and use it to infer division-of-labor mechanisms from single-cell RNA sequencing (RNA-seq) and spatial transcriptomics data of stromal, epithelial, and immune cells. Our framework can be used to characterize the complexity of cell interactions within tissues. Division of labor theory predicts distinct, mechanism-dependent spatial patterns Spatial proximity of specialist cells suggests involvement of cell interactions Archetype crosstalk networks reveal patterns of interactions between specialist cells Enterocytes and fibroblasts exemplify distinct division of labor strategies Two of the mechanisms that can drive division of labor in tissues are external signaling gradients and cell-cell interactions. Theory for optimal task allocation explains how to distinguish between the two strategies in single-cell and spatial omics data. This is demonstrated for colon fibroblasts, intestinal enterocytes, lung fibroblasts, and macrophages.
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影响因子：
64.8
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
通讯作者：
Itzkovitz S
影响因子：
3
作者：
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影响因子：
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作者：
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Zhang F
DOI：
10.1038/s41577-019-0131-x
发表时间：
2019-04
期刊：
Nature reviews. Immunology
影响因子：
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作者：
Altan-Bonnet G;Mukherjee R
通讯作者：
Mukherjee R
单细胞分析揭示成纤维细胞异质性以及成纤维细胞和壁细胞识别和区分的标准
影响因子：
16.6
作者：
Muhl, Lars;Genove, Guillem;Betsholtz, Christer
通讯作者：
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