Organoid cell fate dynamics in space and time

Xuan Zheng, Max A Betjes, Pascal Ender, Yvonne J Goos, Guizela Huelsz-Prince, Hans Clevers, Jeroen S van Zon, Sander J Tans

Research output: Contribution to journal/periodicalArticleScientificpeer-review

1 Citation (Scopus)

Abstract

Organoids are a major new tool to study tissue renewal. However, characterizing the underlying differentiation dynamics remains challenging. Here, we developed TypeTracker, which identifies cell fates by AI-enabled cell tracking and propagating end point fates back along the branched lineage trees. Cells that ultimately migrate to the villus commit to their new type early, when still deep inside the crypt, with important consequences: (i) Secretory cells commit before terminal division, with secretory fates emerging symmetrically in sister cells. (ii) Different secretory types descend from distinct stem cell lineages rather than an omnipotent secretory progenitor. (iii) The ratio between secretory and absorptive cells is strongly affected by proliferation after commitment. (iv) Spatial patterning occurs after commitment through type-dependent cell rearrangements. This "commit-then-sort" model contrasts with the conventional conveyor belt picture, where cells differentiate by moving up the crypt-villus axis and hence raises new questions about the underlying commitment and sorting mechanisms.

Original languageEnglish
Pages (from-to)eadd6480
JournalScience advances
Volume9
Issue number33
DOIs
Publication statusPublished - 18 Aug 2023

Keywords

  • Cell Differentiation
  • Organoids
  • Cell Lineage
  • Biological Transport
  • Cell Movement

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