Organoid cell fate dynamics in space and time

TY - JOUR

T1 - Organoid cell fate dynamics in space and time

AU - Zheng, Xuan

AU - Betjes, Max A

AU - Ender, Pascal

AU - Goos, Yvonne J

AU - Huelsz-Prince, Guizela

AU - Clevers, Hans

AU - van Zon, Jeroen S

AU - Tans, Sander J

PY - 2023/8/18

Y1 - 2023/8/18

N2 - 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.

AB - 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.

KW - Cell Differentiation

KW - Organoids

KW - Cell Lineage

KW - Biological Transport

KW - Cell Movement

U2 - 10.1126/sciadv.add6480

DO - 10.1126/sciadv.add6480

M3 - Article

C2 - 37595032

SN - 2375-2548

VL - 9

SP - eadd6480

JO - Science advances

JF - Science advances

IS - 33

ER -