Interkinetic nuclear migration and basal tethering facilitates post-mitotic daughter separation in intestinal organoids.
Interkinetic nuclear migration and basal tethering facilitates post-mitotic daughter separation in intestinal organoids.
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DOI：
10.1242/jcs.211656
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发表时间：
2017-11-15
影响因子：
4
通讯作者：
Näthke I
中科院分区：
文献类型：
--
作者：
Carroll TD;Langlands AJ;Osborne JM;Newton IP;Appleton PL;Näthke I
更新组织的稳态需要平衡的增殖、分化和运动。这在肠上皮中特别重要，其中谱系追踪表明随机分化选择与细胞相对于小生境的位置错综复杂地耦合。为了确定位置是如何实现的，我们跟踪了肠道类器官中的增殖细胞，发现有丝分裂姐妹篇的行为预测了长期定位。我们发现，正常情况下，70%的姐妹篇仍然是邻居，而30%的姐妹在胞质分裂后失去联系并分开。这些有丝分裂后的位置预测较长期的差异所承担的姐妹：相邻的姐妹篇达到类似的位置随着时间的推移，在一对分离的姐妹篇，一个仍然接近其出生地，而另一个是向上移位。计算模拟隐窝动力学证实，有丝分裂后的分离导致姐妹篇到达不同的车厢。我们发现，interkinetic核迁移，细胞的大小和不对称的拴系从细胞的基底侧延伸的过程有助于分离。这些过程在腺瘤性结肠息肉病（Apc）突变上皮中发生改变，其中分离丢失。我们的结论是，有丝分裂后的位置有助于随机小生境退出，当有缺陷时，支持Apc突变细胞的克隆扩增。 有丝分裂子体在肠上皮中的长期位置与它们在有丝分裂后立即放置的位置相关。出生时最初的分离，预示着以后更多的分歧立场。
Homeostasis of renewing tissues requires balanced proliferation, differentiation and movement. This is particularly important in the intestinal epithelium where lineage tracing suggests that stochastic differentiation choices are intricately coupled to the position of a cell relative to a niche. To determine how position is achieved, we followed proliferating cells in intestinal organoids and discovered that the behaviour of mitotic sisters predicted long-term positioning. We found that, normally, 70% of sisters remain neighbours, while 30% lose contact and separate after cytokinesis. These post-mitotic placements predict longer term differences in positions assumed by sisters: adjacent sisters reach similar positions over time; in a pair of separating sisters, one remains close to its birthplace while the other is displaced upward. Computationally modelling crypt dynamics confirmed that post-mitotic separation leads to sisters reaching different compartments. We show that interkinetic nuclear migration, cell size and asymmetric tethering by a process extending from the basal side of cells contribute to separations. These processes are altered in adenomatous polyposis coli (Apc) mutant epithelia where separation is lost. We conclude that post-mitotic placement contributes to stochastic niche exit and, when defective, supports the clonal expansion of Apc mutant cells. The long-term position of mitotic daughters in the intestinal epithelium correlates with their placement immediately after mitosis. An initial separation at birth, predicts more divergent positions later.
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影响因子：
4.3
作者：
Nelson SA;Li Z;Newton IP;Fraser D;Milne RE;Martin DM;Schiffmann D;Yang X;Dormann D;Weijer CJ;Appleton PL;Näthke IS
通讯作者：
Näthke IS
影响因子：
3.2
作者：
Fleming, Elizabeth S.;Zajac, Mark;Tirnauer, Jennifer S.
通讯作者：
Tirnauer, Jennifer S.
影响因子：
9.8
作者：
Langlands, Alistair J.;Almet, Axel A.;Nathke, Inke S.
通讯作者：
Nathke, Inke S.
影响因子：
7.5
作者：
McCartney, Brooke M.;Nathke, Inke S.
通讯作者：
Nathke, Inke S.
影响因子：
7.8
作者：
Bellis, Julien;Duluc, Isabelle;De Mey, Jan R.
通讯作者：
De Mey, Jan R.