Correction of aberrant growth preserves tissue homeostasis

被引：117

作者：

Brown, Samara ^{[1
]}

Pineda, Cristiana M. ^{[1
]}

Xin, Tianchi ^{[1
]}

Boucher, Jonathan ^{[1
]}

Suozzi, Kathleen C. ^{[1
]}

Park, Sangbum ^{[1
]}

Matte-Martone, Catherine ^{[1
]}

Gonzalez, David G. ^{[1
]}

Rytlewski, Julie ^{[2
]}

Beronja, Slobodan ^{[2
]}

Greco, Valentina ^{[1
,3
,4
,5
,6
]}

机构：

[1] Yale Sch Med, Dept Genet, New Haven, CT 06510 USA

[2] Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA 98109 USA

[3] Yale Sch Med, Yale Stem Cell Ctr, New Haven, CT 06510 USA

[4] Yale Sch Med, Yale Canc Ctr, New Haven, CT 06510 USA

[5] Yale Sch Med, Dept Dermatol, New Haven, CT 06510 USA

[6] Yale Sch Med, Dept Cell Biol, New Haven, CT 06510 USA

来源：

NATURE | 2017年 / 548卷 / 7667期

基金：

美国国家卫生研究院;

关键词：

HAIR-FOLLICLE; BETA-CATENIN; STEM-CELL; MUTATIONS; ACTIVATION; MICE; EXPRESSION; NICHE;

D O I：

10.1038/nature23304

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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(1-3). 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/beta-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 mutationin-dependent 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.

引用

页码：334 / +

页数：15

共 35 条

[1] The Wnt secretion protein Evi/Gpr177 promotes glioma tumourigenesis [J].