The epidermal circadian clock integrates and subverts brain signals to guarantee skin homeostasis

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• dc.contributor.author Mortimer, Thomas
• dc.contributor.author Zinna, Valentina M.
• dc.contributor.author Atalay, Muge
• dc.contributor.author Laudanna, Carmelo
• dc.contributor.author Deryagin, Oleg
• dc.contributor.author Posas, Guillem
• dc.contributor.author Smith, Jacob G.
• dc.contributor.author García Lara, Elisa
• dc.contributor.author Vaca Dempere, Mireia, 1994-
• dc.contributor.author Monteiro de Assis, Leonardo Vinícius
• dc.contributor.author Heyde, Isabel
• dc.contributor.author Koronowski, Kevin B.
• dc.contributor.author Petrus, Paul
• dc.contributor.author Greco, Carolina M.
• dc.contributor.author Forrow, Stephen
• dc.contributor.author Oster, Henrik
• dc.contributor.author Sassone-Corsi, Paolo
• dc.contributor.author Welz, Patrick-Simon
• dc.contributor.author Muñoz Cánoves, Pura, 1962-
• dc.contributor.author Aznar Benitah, Salvador
• dc.date.accessioned 2024-10-17T06:04:34Z
• dc.date.embargoEnd info:eu-repo/date/embargoEnd/2025-05-02
• dc.date.issued 2024
• dc.description.abstract In mammals, the circadian clock network drives daily rhythms of tissue-specific homeostasis. To dissect daily inter-tissue communication, we constructed a mouse minimal clock network comprising only two nodes: the peripheral epidermal clock and the central brain clock. By transcriptomic and functional characterization of this isolated connection, we identified a gatekeeping function of the peripheral tissue clock with respect to systemic inputs. The epidermal clock concurrently integrates and subverts brain signals to ensure timely execution of epidermal daily physiology. Timely cell-cycle termination in the epidermal stem cell compartment depends upon incorporation of clock-driven signals originating from the brain. In contrast, the epidermal clock corrects or outcompetes potentially disruptive feeding-related signals to ensure the optimal timing of DNA replication. Together, we present an approach for cataloging the systemic dependencies of daily temporal organization in a tissue and identify an essential gate-keeping function of peripheral circadian clocks that guarantees tissue homeostasis.
• dc.description.sponsorship We thank the genomics units at the CNAG and CRG for assistance with RNA sequencing, Prof. Gregor Eichele for generously providing us with the Syt10-Cre mice, and Veronica Raker for proofreading the manuscript. The authors acknowledge the following funding sources: SAB - European Research Council under the European Union’s Horizon 2020 (H2020) research and innovation programme (Grant agreement No. 787041), the Government of Cataluña (SGR grant), the Government of Spain (MINECO) and the Foundation Lilliane Bettencourt. The IRB Barcelona is a Severo Ochoa Center of Excellence (MINECO award SEV-2015-0505). CMG - H2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement 749869. KBK - NIH F32 (Fellowship DK121425). PMC - MICINN-RTI2018-096068, ERC-2016-AdG-741966, LaCaixa-HEALTH-HR17-00040, MDA, UPGRADE-H2020-825825, AFM, DPP-Spain, Fundació La MaratóTV3-80/19-202021, MWRF, and María-de-Maeztu Program for Units of Excellence to UPF (MDM-2014-0370) and the Severo- Ochoa Program for Centers of Excellence to CNIC (SEV-2015-0505). PP - Wenner-Gren foundations, The foundation Blanceflor, Tore Nilsons foundation and the Novo Nordisk foundation. PSW - RYC2019-026661-I funded by MCIN/AEI/10.13039/501100011033, "ESF Investing in your future", PID2020-113317RA-I00 funded by MCIN/AEI/ 10.13039/501100011033, and by the BBVA Foundation. TM - H2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 754510. VMZ - “la Caixa” INPhINIT Fellowship Grant for Doctoral Studies at Spanish Research Centers of Excellence, “la Caixa'' Foundation, Barcelona (ID 100010434, fellowship LCF/BQ/IN17/11620018). The project has received funding from the H2020 research and innovation program (Marie Skłodowska-Curie grant agreement no. 713673). HO - the German Research Foundation (DFG) -CRC296/TP13.
• dc.embargo.liftdate 2025-05-02
• dc.format.mimetype application/pdf
• dc.identifier.citation Mortimer T, Zinna VM, Atalay M, Laudanna C, Deryagin O, Posas G, et al. The epidermal circadian clock integrates and subverts brain signals to guarantee skin homeostasis. Cell Stem Cell. 2024 Jun 6;31(6):834-49.e4. DOI: 10.1016/j.stem.2024.04.013
• dc.identifier.doi http://dx.doi.org/10.1016/j.stem.2024.04.013
• dc.identifier.issn 1934-5909
• dc.identifier.uri http://hdl.handle.net/10230/61508
• dc.language.iso eng
• dc.publisher Elsevier
• dc.relation.ispartof Cell Stem Cell. 2024 Jun 6;31(6):834-49.e4
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/787041
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/749869
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/741966
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/825825
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2020-113317RA-I00
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/754510
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/713673
• dc.rights © Elsevier http://dx.doi.org/10.1016/j.stem.2024.04.013
• dc.rights.accessRights info:eu-repo/semantics/embargoedAccess
• dc.subject.keyword Aging
• dc.subject.keyword Circadian
• dc.subject.keyword Homeostasis
• dc.subject.keyword Peripheral clocks
• dc.subject.keyword Stem cells
• dc.subject.keyword Systemic communication
• dc.title The epidermal circadian clock integrates and subverts brain signals to guarantee skin homeostasis
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/acceptedVersion