The tumor suppressor Apc controls planar cell polarities central to gut homeostasis
The tumor suppressor Apc controls planar cell polarities central to gut homeostasis
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DOI：
10.1083/jcb.201204086
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发表时间：
2012-08-06
影响因子：
7.8
通讯作者：
De Mey, Jan R.
中科院分区：
文献类型：
--
作者：
Bellis, Julien;Duluc, Isabelle;De Mey, Jan R.
位于肠腺底部的干细胞与支持小生境的细胞紧密接触，为肠上皮的非凡组织更新提供能量。它们的命运是受种群不对称性随机调节的，但不对称命运作为SC分裂的一种模式是否相关，SC生态位是否包含专门细胞类型的定向祖细胞正在争论中。我们展示了纺锤体排列和平面细胞极性，这形成了一个新的功能单元，在SC中，可以产生子细胞各向异性运动远离利基支持细胞。我们认为这有助于SC的稳态。重要的是，我们证明了一些SC分裂是不对称的细胞命运，并提供数据表明，在一些SC，mNumb显示不对称分离。其中一些过程在携带生殖系Apc突变的小鼠的明显正常的隐窝和微腺瘤中发生了改变，为结直肠癌进展的第一阶段提供了新的线索。
The stem cells (SCs) at the bottom of intestinal crypts tightly contact niche-supporting cells and fuel the extraordinary tissue renewal of intestinal epithelia. Their fate is regulated stochastically by populational asymmetry, yet whether asymmetrical fate as a mode of SC division is relevant and whether the SC niche contains committed progenitors of the specialized cell types are under debate. We demonstrate spindle alignments and planar cell polarities, which form a novel functional unit that, in SCs, can yield daughter cell anisotropic movement away from niche-supporting cells. We propose that this contributes to SC homeostasis. Importantly, we demonstrate that some SC divisions are asymmetric with respect to cell fate and provide data suggesting that, in some SCs, mNumb displays asymmetric segregation. Some of these processes were altered in apparently normal crypts and microadenomas of mice carrying germline Apc mutations, shedding new light on the first stages of progression toward colorectal cancer.