[PDF][PDF] Continuum of gene-expression profiles provides spatial division of labor within a differentiated cell type

M Adler, YK Kohanim, A Tendler, A Mayo, U Alon - Cell systems, 2019 - cell.com
Cell systems, 2019cell.com
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 continuum provides 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 …
Summary
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 continuum provides 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.
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