AMOLF, Amsterdam, Netherlands.
Oncode Institute, Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center, Uppsalalaan 8, Utrecht 3584 CT, Netherlands.
Sci Adv. 2023 Aug 18;9(33):eadd6480. doi: 10.1126/sciadv.add6480.
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.
类器官是研究组织更新的重要新工具。然而，描述潜在的分化动力学仍然具有挑战性。在这里，我们开发了 TypeTracker，它通过人工智能驱动的细胞跟踪来识别细胞命运，并沿着分支谱系树传播终点命运。最终迁移到绒毛的细胞在早期就确定了它们的新类型，此时它们仍然在隐窝深处，这具有重要的意义：（i）分泌细胞在终末分裂之前就确定了命运，分泌命运在姐妹细胞中对称出现。（ii）不同的分泌类型来自不同的干细胞谱系，而不是全能的分泌祖细胞。（iii）细胞分化后，细胞增殖强烈影响分泌细胞和吸收细胞的比例。（iv）通过依赖于类型的细胞重排，空间模式在分化后发生。这种“先确定再分类”的模型与传统的输送带模型形成对比，在输送带模型中，细胞通过沿着隐窝-绒毛轴向上移动而分化，这就提出了关于潜在的确定和分类机制的新问题。
