Continuum of Gene-Expression Profiles Provides Spatial Division of Labor within a Differentiated Cell Type

Miri Adler, Yael Korem Kohanim, Avichai Tendler, Avi Mayo, Uri Alon*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)43-52.e5
JournalCell Systems
Volume8
Issue number1
DOIs
StatePublished - 23 Jan 2019
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2018 Elsevier Inc.

Keywords

  • dimensionality reduction
  • enterocytes
  • liver lobule
  • multi-objective optimality
  • pareto-optimality
  • single-cell RNA-seq
  • single-cell transcriptomics
  • systems biology
  • tissue biology

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