Correction of aberrant growth preserves tissue homeostasis.
Correction of aberrant growth preserves tissue homeostasis.
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DOI：
10.1038/nature23304
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发表时间：
2017-08-17
期刊：
影响因子：
64.8
通讯作者：
Greco V
中科院分区：
文献类型：
--
作者：
Brown S;Pineda CM;Xin T;Boucher J;Suozzi KC;Park S;Matte-Martone C;Gonzalez DG;Rytlewski J;Beronja S;Greco V
健康组织中的细胞以惊人的频率获得突变。这些突变中的许多与异常细胞行为如分化缺陷和过度增殖相关，但不能产生肉眼可检测的表型。目前尚不清楚组织如何保持表型正常，尽管存在这些突变细胞。在这里，我们使用活体成像来跟踪负载不同数量的活化Wnt/β-catenin干细胞的小鼠皮肤上皮的命运。我们发现，所有由此产生的生长变形皮肤组织结构退化，无论其大小。野生型细胞是从组织中主动消除突变细胞所必需的，同时利用内源性和异位细胞行为来拆除异常结构。回归后，剩余的结构要么完全消除，要么以生态位依赖的方式转化为功能性皮肤附件。此外，由致癌Hras产生的组织异常，甚至组织的突变无关性变形也可以被校正，这表明这种耐受现象反映了皮肤中的保守原理。这项研究揭示了一个意想不到的可塑性的成人皮肤上皮细胞时，面对突变和非突变的侮辱，并阐明了动态的细胞行为用于其返回到稳态。
Cells in healthy tissues acquire mutations with surprising frequency. Many of these mutations are associated with abnormal cellular behaviours such as differentiation defects and hyperproliferation, yet fail to produce macroscopically detectable phenotypes. It is currently unclear how the tissue remains phenotypically normal, despite the presence of these mutant cells. Here we use intravital imaging to track the fate of mouse skin epithelium burdened with varying numbers of activated Wnt/β-catenin stem cells. We show that all resulting growths that deform the skin tissue architecture regress, irrespective of their size. Wild-type cells are required for the active elimination of mutant cells from the tissue, while utilizing both endogenous and ectopic cellular behaviours to dismantle the aberrant structures. After regression, the remaining structures are either completely eliminated or converted into functional skin appendages in a niche-dependent manner. Furthermore, tissue aberrancies generated from oncogenic Hras, and even mutation-independent deformations to the tissue, can also be corrected, indicating that this tolerance phenomenon reflects a conserved principle in the skin. This study reveals an unanticipated plasticity of the adult skin epithelium when faced with mutational and non-mutational insult, and elucidates the dynamic cellular behaviours used for its return to a homeostatic state.
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影响因子：
64.5
作者：
Fujiwara H;Ferreira M;Donati G;Marciano DK;Linton JM;Sato Y;Hartner A;Sekiguchi K;Reichardt LF;Watt FM
通讯作者：
Watt FM
影响因子：
30.8
作者：
Laurie, Cathy C.;Laurie, Cecelia A.;Rice, Kenneth;Doheny, Kimberly F.;Zelnick, Leila R.;McHugh, Caitlin P.;Ling, Hua;Hetrick, Kurt N.;Pugh, Elizabeth W.;Amos, Chris;Wei, Qingyi;Wang, Li-E;Lee, Jeffrey E.;Barnes, Kathleen C.;Hansel, Nadia N.;Mathias, Rasika;Daley, Denise;Beaty, Terri H.;Scott, Alan F.;Ruczinski, Ingo;Scharpf, Rob B.;Bierut, Laura J.;Hartz, Sarah M.;Landi, Maria Teresa;Freedman, Neal D.;Goldin, Lynn R.;Ginsburg, David;Li, Jun;Desch, Karl C.;Strom, Sara S.;Blot, William J.;Signorello, Lisa B.;Ingles, Sue A.;Chanock, Stephen J.;Berndt, Sonja I.;Le Marchand, Loic;Henderson, Brian E.;Monroe, Kristine R.;Heit, John A.;de Andrade, Mariza;Armasu, Sebastian M.;Regnier, Cynthia;Lowe, William L.;Hayes, M. Geoffrey;Marazita, Mary L.;Feingold, Eleanor;Murray, Jeffrey C.;Melbye, Mads;Feenstra, Bjarke;Kang, Jae H.;Wiggs, Janey L.;Jarvik, Gail P.;McDavid, Andrew N.;Seshan, Venkatraman E.;Mirel, Daniel B.;Crenshaw, Andrew;Sharopova, Nataliya;Wise, Anastasia;Shen, Jess;Crosslin, David R.;Levine, David M.;Zheng, Xiuwen;Udren, Jenna I.;Bennett, Siiri;Nelson, Sarah C.;Gogarten, Stephanie M.;Conomos, Matthew P.;Heagerty, Patrick;Manolio, Teri;Pasquale, Louis R.;Haiman, Christopher A.;Caporaso, Neil;Weir, Bruce S.
通讯作者：
Weir, Bruce S.
影响因子：
1.5
作者：
Means, Anna L.;Xu, Yanwen;Gu, Guoqiang
通讯作者：
Gu, Guoqiang
影响因子：
6
作者：
Ling, G;Persson, A;Ponten, F
通讯作者：
Ponten, F
DOI：
10.1126/science.1233029
发表时间：
2013-07-19
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Fuchs Y;Brown S;Gorenc T;Rodriguez J;Fuchs E;Steller H
通讯作者：
Steller H