{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T12:55:38Z","timestamp":1774356938011,"version":"3.50.1"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2021,10,5]],"date-time":"2021-10-05T00:00:00Z","timestamp":1633392000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31930022"],"award-info":[{"award-number":["31930022"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31771476"],"award-info":[{"award-number":["31771476"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["12026608"],"award-info":[{"award-number":["12026608"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["12042104"],"award-info":[{"award-number":["12042104"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["11871456"],"award-info":[{"award-number":["11871456"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Strategic Priority Project of CAS","award":["XDB38040400"],"award-info":[{"award-number":["XDB38040400"]}]},{"name":"National Key R&D Program of China","award":["2017YFA0505500"],"award-info":[{"award-number":["2017YFA0505500"]}]},{"name":"JST Moonshot R&D program","award":["MJMS2021"],"award-info":[{"award-number":["MJMS2021"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,1,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>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 (l-DNB) 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.<\/jats:p>","DOI":"10.1093\/jmcb\/mjab060","type":"journal-article","created":{"date-parts":[[2021,9,30]],"date-time":"2021-09-30T20:15:57Z","timestamp":1633032957000},"page":"822-833","source":"Crossref","is-referenced-by-count":26,"title":["Landscape dynamic network biomarker analysis reveals the tipping point of transcriptome reprogramming to prevent skin photodamage"],"prefix":"10.1093","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8764-2521","authenticated-orcid":false,"given":"Chengming","family":"Zhang","sequence":"first","affiliation":[{"name":"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"},{"name":"University of the Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing 100049, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Unilever Research & Development Centre Shanghai, Shanghai 200335, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Ge","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tingyan","family":"Mi","sequence":"additional","affiliation":[{"name":"Unilever Research & Development Centre Shanghai, Shanghai 200335, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao","family":"Cui","sequence":"additional","affiliation":[{"name":"Unilever Research & Development Centre Shanghai, Shanghai 200335, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fengjuan","family":"Tu","sequence":"additional","affiliation":[{"name":"Unilever Research & Development Centre Shanghai, Shanghai 200335, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuelan","family":"Gu","sequence":"additional","affiliation":[{"name":"Unilever Research & Development Centre Shanghai, Shanghai 200335, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tao","family":"Zeng","sequence":"additional","affiliation":[{"name":"Bio-Med Big Data Center, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3960-0068","authenticated-orcid":false,"given":"Luonan","family":"Chen","sequence":"additional","affiliation":[{"name":"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"},{"name":"School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China"},{"name":"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"},{"name":"Guangdong Institute of Intelligence Science and Technology, Zhuhai 519031, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2021,10,5]]},"reference":[{"key":"2022012121151422100_mjab060-B1","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.mrfmmm.2004.07.019","article-title":"Photochemoprevention of ultraviolet B signaling and photocarcinogenesis","volume":"571","author":"Afaq","year":"2005","journal-title":"Mutat. Res"},{"key":"2022012121151422100_mjab060-B2","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1016\/j.bbagrm.2014.03.013","article-title":"Myc and cell cycle control","volume":"1849","author":"Bretones","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"2022012121151422100_mjab060-B3","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1007\/s10522-017-9715-7","article-title":"Plant extracts and natural compounds used against UVB-induced photoaging","volume":"18","author":"Cavinato","year":"2017","journal-title":"Biogerontology"},{"key":"2022012121151422100_mjab060-B4","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1038\/srep00342","article-title":"Detecting early-warning signals for sudden deterioration of complex diseases by dynamical network biomarkers","volume":"2","author":"Chen","year":"2012","journal-title":"Sci. Rep"},{"key":"2022012121151422100_mjab060-B5","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.1038\/jid.2010.5","article-title":"Regulation of human skin pigmentation in situ by repetitive UV exposure: molecular characterization of responses to UVA and\/or UVB","volume":"130","author":"Choi","year":"2010","journal-title":"J. Invest. Dermatol"},{"key":"2022012121151422100_mjab060-B6","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1007\/s00428-019-02533-9","article-title":"\u03b2-Catenin nuclear expression discriminates deep penetrating nevi from other cutaneous melanocytic tumors","volume":"474","author":"de la Fouchardiere","year":"2019","journal-title":"Virchows Arch"},{"key":"2022012121151422100_mjab060-B7","first-page":"72","article-title":"Vitis vinifera seeds extract for the modulation of cytosolic factors BAX-\u03b1 and NF-\u03baB involved in UVB-induced oxidative stress and apoptosis of human skin cells","volume":"89","author":"Decean","year":"2016","journal-title":"Clujul. Med"},{"key":"2022012121151422100_mjab060-B8","doi-asserted-by":"crossref","first-page":"12222","DOI":"10.3390\/ijms140612222","article-title":"UV radiation and the skin","volume":"14","author":"D'Orazio","year":"2013","journal-title":"Int. J. Mol. Sci"},{"key":"2022012121151422100_mjab060-B9","doi-asserted-by":"crossref","first-page":"1641","DOI":"10.1093\/bib\/bbz089","article-title":"Network control principles for identifying personalized driver genes in cancer","volume":"21","author":"Guo","year":"2020","journal-title":"Brief. Bioinform"},{"key":"2022012121151422100_mjab060-B10","doi-asserted-by":"crossref","first-page":"42990","DOI":"10.1038\/srep42990","article-title":"TWIST1 induces MMP3 expression through up-regulating DNA hydroxymethylation and promotes catabolic responses in human chondrocytes","volume":"7","author":"Hasei","year":"2017","journal-title":"Sci. Rep"},{"key":"2022012121151422100_mjab060-B12","doi-asserted-by":"crossref","first-page":"8498","DOI":"10.1038\/s41598-018-26438-w","article-title":"Unravelling miRNA regulation in yield of rice (Oryza sativa) based on differential network model","volume":"8","author":"Hu","year":"2018","journal-title":"Sci. Rep"},{"key":"2022012121151422100_mjab060-B13","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/j.gpb.2019.11.007","article-title":"Identification of key genes for the ultrahigh yield of rice using dynamic cross-tissue network analysis","volume":"18","author":"Hu","year":"2020","journal-title":"Genomics Proteomics Bioinform"},{"key":"2022012121151422100_mjab060-B14","doi-asserted-by":"crossref","first-page":"e29241","DOI":"10.1371\/journal.pone.0029241","article-title":"Repeated small perturbation approach reveals transcriptomic steady states","volume":"6","author":"Huang","year":"2011","journal-title":"PLoS One"},{"key":"2022012121151422100_mjab060-B15","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1016\/j.scib.2020.01.013","article-title":"SMAD7 and SERPINE1 as novel dynamic network biomarkers detect and regulate the tipping point of TGF-\u03b2 induced EMT","volume":"65","author":"Jiang","year":"2020","journal-title":"Sci. Bull"},{"key":"2022012121151422100_mjab060-B16","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1111\/1523-1747.ep12319308","article-title":"E2F as a regulator of keratinocyte proliferation: implications for skin tumor development","volume":"109","author":"Jones","year":"1997","journal-title":"J. Invest. Dermatol"},{"key":"2022012121151422100_mjab060-B11","doi-asserted-by":"crossref","first-page":"1692","DOI":"10.1038\/jid.2011.109","article-title":"Transcriptional profiling shows altered expression of Wnt pathway- and lipid metabolism-related genes as well as melanogenesis-related genes in melasma","volume":"131","author":"Kang","year":"2011","journal-title":"J. Invest. Dermat"},{"key":"2022012121151422100_mjab060-B17","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1111\/acel.12087","article-title":"Implications of time-series gene expression profiles of replicative senescence","volume":"12","author":"Kim","year":"2013","journal-title":"Aging Cell"},{"key":"2022012121151422100_mjab060-B18","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1093\/bib\/bbt027","article-title":"Detecting tissue-specific early warning signals for complex diseases based on dynamical network biomarkers: study of type 2 diabetes by cross-tissue analysis","volume":"15","author":"Li","year":"2014","journal-title":"Brief. Bioinform"},{"key":"2022012121151422100_mjab060-B19","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.plrev.2021.04.002","article-title":"Collective fluctuation implies imminent state transition: comment on \u2018Dynamic and thermodynamic models of adaptation\u2019 by A.N. Gorban et al","volume":"37","author":"Liu","year":"2021","journal-title":"Phys. Life Rev"},{"key":"2022012121151422100_mjab060-B20","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1038\/srep00813","article-title":"Identifying critical transitions and their leading biomolecular networks in complex diseases","volume":"2","author":"Liu","year":"2012","journal-title":"Sci. Rep"},{"key":"2022012121151422100_mjab060-B21","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/med.21293","article-title":"Early diagnosis of complex diseases by molecular biomarkers, network biomarkers, and dynamical network biomarkers","volume":"34","author":"Liu","year":"2014","journal-title":"Med. Res. Rev"},{"key":"2022012121151422100_mjab060-B22","article-title":"Predicting local COVID-19 outbreaks and infectious disease epidemics based on landscape network entropy","author":"Liu","year":"2021","journal-title":"Sci. Bull."},{"key":"2022012121151422100_mjab060-B23","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1093\/nsr\/nwy162","article-title":"Detection for disease tipping points by landscape dynamic network biomarkers","volume":"6","author":"Liu","year":"2019","journal-title":"Natl Sci. Rev"},{"key":"2022012121151422100_mjab060-B24","doi-asserted-by":"crossref","first-page":"e164","DOI":"10.1093\/nar\/gkw772","article-title":"Personalized characterization of diseases using sample-specific networks","volume":"44","author":"Liu","year":"2016","journal-title":"Nucleic Acids Res"},{"key":"2022012121151422100_mjab060-B25","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1016\/j.molcel.2018.09.022","article-title":"UV-protection timer controls linkage between stress and pigmentation skin protection systems","volume":"72","author":"Malcov-Brog","year":"2018","journal-title":"Mol. Cell"},{"key":"2022012121151422100_mjab060-B26"},{"key":"2022012121151422100_mjab060-B27","doi-asserted-by":"crossref","first-page":"2585","DOI":"10.1038\/sj.jid.5700902","article-title":"Gene expression time course in the human skin during elicitation of allergic contact dermatitis","volume":"127","author":"Pedersen","year":"2007","journal-title":"J. Invest. Dermatol"},{"key":"2022012121151422100_mjab060-B28","doi-asserted-by":"crossref","first-page":"e7651","DOI":"10.1371\/journal.pone.0007651","article-title":"Dynamic and physical clustering of gene expression during epidermal barrier formation in differentiating keratinocytes","volume":"4","author":"Taylor","year":"2009","journal-title":"PLoS One"},{"key":"2022012121151422100_mjab060-B29","doi-asserted-by":"crossref","first-page":"634","DOI":"10.3109\/10799893.2015.1041646","article-title":"Down-regulation of TGF-b1, TGF-b receptor 2, and TGF-b-associated microRNAs, miR-20a and miR-21, in skin lesions of sulfur mustard-exposed Iranian war veterans","volume":"35","author":"Valizadeh","year":"2015","journal-title":"J. Recept. Signal. Transduct. Res"},{"key":"2022012121151422100_mjab060-B30","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1093\/aje\/kwj137","article-title":"Expression of p53 tumor suppressor protein in sun-exposed skin and associations with sunscreen use and time spent outdoors: a community-based study","volume":"163","author":"van der Pols","year":"2006","journal-title":"Am. J. Epidemiol"},{"key":"2022012121151422100_mjab060-B31","doi-asserted-by":"crossref","first-page":"6382","DOI":"10.1158\/0008-5472.CAN-12-1033","article-title":"TWIST1 is an ERK1\/2 effector that promotes invasion and regulates MMP-1 expression in human melanoma cells","volume":"72","author":"Weiss","year":"2012","journal-title":"Cancer Res"},{"key":"2022012121151422100_mjab060-B32","doi-asserted-by":"crossref","first-page":"1492","DOI":"10.1159\/000493451","article-title":"A time-series analysis of severe burned injury of skin gene expression profiles","volume":"49","author":"Xu","year":"2018","journal-title":"Cell. Physiol. Biochem"},{"key":"2022012121151422100_mjab060-B33","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1038\/s41467-018-03024-2","article-title":"Dynamic network biomarker indicates pulmonary metastasis at the tipping point of hepatocellular carcinoma","volume":"9","author":"Yang","year":"2018","journal-title":"Nat. Commun"},{"key":"2022012121151422100_mjab060-B34","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1136\/gutjnl-2015-310318","article-title":"Interferon\u2013microRNA signalling drives liver precancerous lesion formation and hepatocarcinogenesis","volume":"65","author":"Yang","year":"2016","journal-title":"Gut"},{"key":"2022012121151422100_mjab060-B35","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.taap.2013.03.015","article-title":"Quercitrin protects skin from UVB-induced oxidative damage","volume":"269","author":"Yin","year":"2013","journal-title":"Toxicol. Appl. Pharmacol"},{"key":"2022012121151422100_mjab060-B36","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1186\/s12967-015-0546-5","article-title":"Unravelling personalized dysfunctional gene network of complex diseases based on differential network model","volume":"13","author":"Yu","year":"2015","journal-title":"J. Transl. Med"},{"key":"2022012121151422100_mjab060-B37","doi-asserted-by":"crossref","first-page":"5682","DOI":"10.1111\/febs.12536","article-title":"Network biomarkers reveal dysfunctional gene regulations during disease progression","volume":"280","author":"Zeng","year":"2013","journal-title":"FEBS J"},{"key":"2022012121151422100_mjab060-B38","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/j.ymeth.2014.01.021","article-title":"Deciphering early development of complex diseases by progressive module network","volume":"67","author":"Zeng","year":"2014","journal-title":"Methods"},{"key":"2022012121151422100_mjab060-B39","doi-asserted-by":"crossref","first-page":"6851464","DOI":"10.1155\/2017\/6851464","article-title":"Echinacoside alleviates UVB irradiation-mediated skin damage via inhibition of oxidative stress, DNA damage, and apoptosis","volume":"2017","author":"Zhang","year":"2017","journal-title":"Oxid. Med. Cell Longev"}],"container-title":["Journal of Molecular Cell Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jmcb\/advance-article-pdf\/doi\/10.1093\/jmcb\/mjab060\/40509673\/mjab060.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jmcb\/article-pdf\/13\/11\/822\/42256827\/mjab060.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jmcb\/article-pdf\/13\/11\/822\/42256827\/mjab060.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,21]],"date-time":"2022-01-21T22:43:27Z","timestamp":1642805007000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jmcb\/article\/13\/11\/822\/6381584"}},"subtitle":[],"editor":[{"given":"Jiarui","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2021,10,5]]},"references-count":39,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2021,10,5]]},"published-print":{"date-parts":[[2022,1,21]]}},"URL":"https:\/\/doi.org\/10.1093\/jmcb\/mjab060","relation":{},"ISSN":["1759-4685"],"issn-type":[{"value":"1759-4685","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,11,1]]},"published":{"date-parts":[[2021,10,5]]}}}