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Finger AM, Jäschke S, Del Olmo M, et al. Intercellular coupling between peripheral circadian oscillators by TGF-β signaling. Sci Adv. 2021;7(30)doi: 10.1126/sciadv.abg5174.
Finger, A. M., Jäschke, S., Del Olmo, M., Hurwitz, R., Granada, A. E., Herzel, H., & Kramer, A. (2021). Intercellular coupling between peripheral circadian oscillators by TGF-β signaling. Science advances, 7(30), . https://doi.org/10.1126/sciadv.abg5174
Finger, Anna-Marie, et al. "Intercellular coupling between peripheral circadian oscillators by TGF-β signaling." Science advances vol. 7,30 (2021). doi: https://doi.org/10.1126/sciadv.abg5174
Finger AM, Jäschke S, Del Olmo M, Hurwitz R, Granada AE, Herzel H, Kramer A. Intercellular coupling between peripheral circadian oscillators by TGF-β signaling. Sci Adv. 2021 Jul 23;7(30). doi: 10.1126/sciadv.abg5174. Print 2021 Jul. PMID: 34301601; PMCID: PMC8302137.
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Sci Adv. 2021 Jul 23;7(30). doi: 10.1126/sciadv.abg5174. Print 2021 Jul.

Intercellular coupling between peripheral circadian oscillators by TGF-β signaling.

Science advances

Anna-Marie Finger, Sebastian Jäschke, Marta Del Olmo, Robert Hurwitz, Adrián E Granada, Hanspeter Herzel, Achim Kramer

Affiliations

  1. Charité Universitätsmedizin Berlin, Institute for Medical Immunology, Laboratory of Chronobiology, Charitéplatz 1, 10117 Berlin, Germany. [email protected] [email protected].
  2. Berlin Institute of Health (BIH), Berlin, Germany.
  3. Charité Universitätsmedizin Berlin, Institute for Medical Immunology, Laboratory of Chronobiology, Charitéplatz 1, 10117 Berlin, Germany.
  4. Charité and Humboldt Universität zu Berlin, Institute for Theoretical Biology, Laboratory of Theoretical Chronobiology, Philippstraße 13, 10115 Berlin, Germany.
  5. Max Planck Institute for Infection Biology, Biochemistry-Protein Purification Core Facility, Charitéplatz 1, 10117 Berlin, Germany.
  6. Charité-Universitätsmedizin, Charité Comprehensive Cancer Center, Laboratory of Systems Oncology, Charitéplatz 1, 10117 Berlin, Germany.
  7. German Cancer Consortium (DKTK), German Cancer Research Center, Partner Site Berlin, 69120, Heidelberg, Germany.

PMID: 34301601 PMCID: PMC8302137 DOI: 10.1126/sciadv.abg5174

Abstract

Coupling between cell-autonomous circadian oscillators is crucial to prevent desynchronization of cellular networks and disruption of circadian tissue functions. While neuronal oscillators within the mammalian central clock, the suprachiasmatic nucleus, couple intercellularly, coupling among peripheral oscillators is controversial and the molecular mechanisms are unknown. Using two- and three-dimensional mammalian culture models in vitro (mainly human U-2 OS cells) and ex vivo, we show that peripheral oscillators couple via paracrine pathways. We identify transforming growth factor-β (TGF-β) as peripheral coupling factor that mediates paracrine phase adjustment of molecular clocks through transcriptional regulation of core-clock genes. Disruption of TGF-β signaling causes desynchronization of oscillator networks resulting in reduced amplitude and increased sensitivity toward external zeitgebers. Our findings reveal an unknown mechanism for peripheral clock synchrony with implications for rhythmic organ functions and circadian health.

Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).

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