Emergence of division of labor in tissues through cell interactions and spatial cues
Miri Adler,
Noa Moriel,
Aleksandrina Goeva,
Inbal Avraham-Davidi,
Simon Mages,
Taylor S. Adams,
Naftali Kaminski,
Evan Z. Macosko,
Aviv Regev,
Ruslan Medzhitov,
Mor Nitzan
Affiliations
Miri Adler
Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA; Tananbaum Center for Theoretical and Analytical Human Biology, Yale University School of Medicine, New Haven, CT, USA
Noa Moriel
School of Computer Science and Engineering, The Hebrew University of Jerusalem, Jerusalem, Israel
Aleksandrina Goeva
Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA
Inbal Avraham-Davidi
Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA
Simon Mages
Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA; Gene Center and Department of Biochemistry, Ludwig-Maximilians-University Munich, Munich, Germany
Taylor S. Adams
Section of Pulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, New Haven, CT, USA
Naftali Kaminski
Section of Pulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, New Haven, CT, USA
Evan Z. Macosko
Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA; Massachusetts General Hospital, Department of Psychiatry, Boston, MA, USA
Aviv Regev
Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA; Corresponding author
Ruslan Medzhitov
Tananbaum Center for Theoretical and Analytical Human Biology, Yale University School of Medicine, New Haven, CT, USA; Howard Hughes Medical Institute, Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA; Corresponding author
Mor Nitzan
School of Computer Science and Engineering, The Hebrew University of Jerusalem, Jerusalem, Israel; Racah Institute of Physics, The Hebrew University of Jerusalem, Jerusalem, Israel; Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel; Corresponding author
Summary: 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.
