Paneth Cell-Rich Regions Separated by a Cluster of Lgr5+Cells Initiate Crypt Fission in the Intestinal Stem Cell Niche
Paneth Cell-Rich Regions Separated by a Cluster of Lgr5+Cells Initiate Crypt Fission in the Intestinal Stem Cell Niche
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DOI：
10.1371/journal.pbio.1002491
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发表时间：
2016-06-01
期刊：
影响因子：
9.8
通讯作者：
Nathke, Inke S.
中科院分区：
文献类型：
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作者：
Langlands, Alistair J.;Almet, Axel A.;Nathke, Inke S.
肠上皮的隐窝容纳了干细胞，以确保肠道上皮细胞的持续更新。地穴数量的增加是通过一个叫做地穴分裂的过程，一个地穴分裂成两个子地穴。裂变驱动正常的组织生长和维持。相应地，它在成年期变得不那么频繁。重要的是，分裂被重新激活以驱动腺瘤生长。人们对裂变的机制知之甚少。然而，只有了解正常的裂变是如何运作的，才能阐明癌症相关的变化。我们使用高分辨率成像研究了三维组织中的正常裂变，并使用肠道类器官来确定潜在的机制。我们发现Paneth细胞和Lgr 5+细胞的数量和相对位置对裂变都很重要。此外，潘氏细胞的较高硬度和增加的粘附性参与决定裂变的位点。在至少两个富含潘氏细胞的结构域之间形成一簇Lgr 5+细胞建立了启动裂变的向上内陷的位点。
The crypts of the intestinal epithelium house the stem cells that ensure the continual renewal of the epithelial cells that line the intestinal tract. Crypt number increases by a process called crypt fission, the division of a single crypt into two daughter crypts. Fission drives normal tissue growth and maintenance. Correspondingly, it becomes less frequent in adulthood. Importantly, fission is reactivated to drive adenoma growth. The mechanisms governing fission are poorly understood. However, only by knowing how normal fission operates can cancer-associated changes be elucidated. We studied normal fission in tissue in three dimensions using high-resolution imaging and used intestinal organoids to identify underlying mechanisms. We discovered that both the number and relative position of Paneth cells and Lgr5+ cells are important for fission. Furthermore, the higher stiffness and increased adhesion of Paneth cells are involved in determining the site of fission. Formation of a cluster of Lgr5+ cells between at least two Paneth-cell-rich domains establishes the site for the upward invagination that initiates fission.