Landscape dynamic network biomarker analysis reveals the tipping point of transcriptome reprogramming to prevent skin photodamage  

作　　者：Chengming Zhang Hong Zhang Jing Ge Tingyan Mi Xiao Cui Fengjuan Tu Xuelan Gu Tao Zeng Luonan Chen 

机构地区：[1]State Key Laboratory of Cell Biology,Shanghai Institute of Biochemistry and Cell Biology,Center for Excellence in Molecular Cell Science,Chinese Academy of Sciences,Shanghai 200031,China [2]University of the Chinese Academy of Sciences,Chinese Academy of Sciences,Beijing 100049,China [3]Unilever Research&Development Centre Shanghai,Shanghai 200335,China [4]Bio-Med Big Data Center,Shanghai Institute of Nutrition and Health,University of Chinese Academy of Sciences,Chinese Academy of Sciences,Shanghai 200031,China [5]School of Life Science and Technology,ShanghaiTech University,Shanghai 201210,China [6]Key Laboratory of Systems Health Science of Zhejiang Province,Hangzhou Institute for Advanced Study,University of Chinese Academy of Sciences,Chinese Academy of Sciences,Hangzhou 310024,China [7]Guangdong Institute of Intelligence Science and Technology,Zhuhai 519031,China

出　　处：《Journal of Molecular Cell Biology》2021年第11期822-833,共12页分子细胞生物学报（英文版）

基　　金：partially supported by the National Natural Science Foundation of China(31930022,31771476,12026608,12042104,and 11871456);the Strategic Priority Project of CAS(XDB38040400);the National Key R&D Program of China(2017YFA0505500);JST Moonshot R&D program(JP MJMS2021 to L.C.).

摘　　要：Skin,as the outmost layer of human body,is frequently exposed to environmental stressors including pollutants and ultraviolet(UV),which could lead to skin disorders.Generally,skin response process to ultraviolet B(UVB)irradiation is a nonlinear dynamic process,with unknown underlying molecular mechanism of critical transition.Here,the landscape dynamic network biomarker(lDNB)analysis of time series transcriptome data on 3D skin model was conducted to reveal the complicated process of skin response to UV irradiation at both molecular and network levels.The advanced l-DNB analysis approach showed that:(i)there was a tipping point before critical transition state during pigmentation process,validated by 3D skin model;(ii)13 core DNB genes were identified to detect the tipping point as a network biomarker,supported by computational assessment;(iii)core DNB genes such as COL7A1 and CTNNB1 can effectively predict skin lightening,validated by independent human skin data.Overall,this study provides new insights for skin response to repetitive UVB irradiation,including dynamic pathway pattern,biphasic response,and DNBs for skin lightening change,and enables us to further understand the skin resilience process after external stress.

关 键 词：single-sample network tipping point UVB irradiation living skin equivalent model time series data skin lightening 

分 类 号：R751[医药卫生—皮肤病学与性病学]