TY - JOUR T1 - Emergence of division of labor in tissues through cell interactions and spatial cues JF - bioRxiv DO - 10.1101/2022.11.16.516540 SP - 2022.11.16.516540 AU - Miri Adler AU - Noa Moriel AU - Aleksandrina Goeva AU - Inbal Avraham-Davidi AU - Simon Mages AU - Taylor S Adams AU - Naftali Kaminski AU - Evan Z Macosko AU - Aviv Regev AU - Ruslan Medzhitov AU - Mor Nitzan Y1 - 2022/01/01 UR - http://biorxiv.org/content/early/2022/11/17/2022.11.16.516540.abstract N2 - 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 vs. 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-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.Competing Interest StatementNK served as a consultant to Boehringer Ingelheim, Third Rock, Pliant, Samumed, NuMedii, Theravance, LifeMax, Three Lake Partners, Optikira, Astra Zeneca, RohBar, Veracyte, Augmanity, CSL Behring, Galapagos, Gilead, Arrowhead and Thyron over the last 3 years, reports Equity in Pliant and Thyron, and a grant from Veracyte, Boehringer Ingelheim, BMS and non- financial support from MiRagen and Astra Zeneca. NK has IP on novel biomarkers and therapeutics in IPF licensed to Biotech. EZM is a consultant for Curio Biosciences, inc. AR is a co-founder and equity holder of Celsius Therapeutics, an equity holder in Immunitas, and was an SAB member of ThermoFisher Scientific, Syros Pharmaceuticals, Neogene Therapeutics and Asimov until July 31, 2020. From August 1, 2020, AR is an employee of Genentech and has equity in Roche. ER -