June (2022-06-30 23:59):
#paper doi: 10.1126/science.aaw9021. Epub 2022 Jan 7.Tissue geometry drives deterministic organoid patterning该研究提出了一种指导基于干细胞的器官发生的方法,该过程完全由“随机”自组织驱动。该研究还验证了长期存在但未充分探索的形态发生范例,其中组织的当前形状可以帮助图案化和指定组织的发育过程,从而确定组织的未来形状。在肠隐窝形成的情况下,出芽不仅可以跟随Paneth细胞的出现,而且还可以先于它。该研究的类器官培养物可用于回答现有类器官和动物模型无法解决的问题,它们可以将类器官技术转化为现实世界的应用。
Tissue geometry drives deterministic organoid patterning
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Abstract:
Epithelial organoids are stem cell–derived tissues that approximate aspects of real organs, and thus they have potential as powerful tools in basic and translational research. By definition, they self-organize, but the structures formed are often heterogeneous and irreproducible, which limits their use in the lab and clinic. We describe methodologies for spatially and temporally controlling organoid formation, thereby rendering a stochastic process more deterministic. Bioengineered stem cell microenvironments are used to specify the initial geometry of intestinal organoids, which in turn controls their patterning and crypt formation. We leveraged the reproducibility and predictability of the culture to identify the underlying mechanisms of epithelial patterning, which may contribute to reinforcing intestinal regionalization in vivo. By controlling organoid culture, we demonstrate how these structures can be used to answer questions not readily addressable with the standard, more variable, organoid models.
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