Notch Signaling and Cross-Talk in Hypoxia: A Candidate Pathway for High-Altitude Adaptation.
O'Brien, Katie A
Simonson, Tatum S
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O'Brien, K. A., Murray, A. J., & Simonson, T. S. (2022). Notch Signaling and Cross-Talk in Hypoxia: A Candidate Pathway for High-Altitude Adaptation.. Life (Basel) https://doi.org/10.3390/life12030437
Hypoxia triggers complex inter- and intracellular signals that regulate tissue oxygen (O2) homeostasis, adjusting convective O2 delivery and utilization (i.e., metabolism). Human populations have been exposed to high-altitude hypoxia for thousands of years and, in doing so, have undergone natural selection of multiple gene regions supporting adaptive traits. Some of the strongest selection signals identified in highland populations emanate from hypoxia-inducible factor (HIF) pathway genes. The HIF pathway is a master regulator of the cellular hypoxic response, but it is not the only regulatory pathway under positive selection. For instance, regions linked to the highly conserved Notch signaling pathway are also top targets, and this pathway is likely to play essential roles that confer hypoxia tolerance. Here, we explored the importance of the Notch pathway in mediating the cellular hypoxic response. We assessed transcriptional regulation of the Notch pathway, including close cross-talk with HIF signaling, and its involvement in the mediation of angiogenesis, cellular metabolism, inflammation, and oxidative stress, relating these functions to generational hypoxia adaptation.
Adaptation, Hypobaric hypoxia, Notch signaling, hypoxia-inducible factor
KAO received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement (No 890768). AJM was funded by the Research Councils UK (EP/E500552/1). TSS was funded by the National Institutes of Health (R01HL145470), National Geographic Explorer Award, and the John B. West Endowed Chair in Respiratory Physiology.
European Commission Horizon 2020 (H2020) Marie Sk?odowska-Curie actions (890768)
External DOI: https://doi.org/10.3390/life12030437
This record's URL: https://www.repository.cam.ac.uk/handle/1810/336439
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/