Organoid cell fate dynamics in space and time

Organoid cell fate dynamics in space and time

Zheng, Xuan (AMOLF)
Betjes, M.A. (AMOLF)
Ender, Pascal (AMOLF)
Goos, Yvonne J. (AMOLF)
Huelsz-Prince, Guizela (AMOLF)
Clevers, Hans (University Medical Center Utrecht; Institute of the Royal Netherlands Academy of Arts and Sciences)
van Zon, Jeroen S. (AMOLF)
Tans, S.J. (TU Delft BN/Sander Tans Lab; Kavli institute of nanoscience Delft; AMOLF)

2023

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.

http://resolver.tudelft.nl/uuid:7425a8ae-dd87-4ebd-a725-d4ac9454d691

https://doi.org/10.1126/sciadv.add6480

2375-2548

Science Advances, 9 (33)

Institutional Repository

journal article

© 2023 Xuan Zheng, M.A. Betjes, Pascal Ender, Yvonne J. Goos, Guizela Huelsz-Prince, Hans Clevers, Jeroen S. van Zon, S.J. Tans