Journal article
Dynamic changes in intracellular ROS levels regulate airway basal stem cell homeostasis through Nrf2-dependent Notch signaling
Cell stem cell, v 15(2), pp 199-214
07 Aug 2014
PMID: 24953182
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Airways are exposed to myriad environmental and damaging agents such as reactive oxygen species (ROS), which also have physiological roles as signaling molecules that regulate stem cell function. However, the functional significance of both steady and dynamically changing ROS levels in different stem cell populations, as well as downstream mechanisms that integrate ROS sensing into decisions regarding stem cell homeostasis, are unclear. Here, we show in mouse and human airway basal stem cells (ABSCs) that intracellular flux from low to moderate ROS levels is required for stem cell self-renewal and proliferation. Changing ROS levels activate Nrf2, which activates the Notch pathway to stimulate ABSC self-renewal and an antioxidant program that scavenges intracellular ROS, returning overall ROS levels to a low state to maintain homeostatic balance. This redox-mediated regulation of lung stem cell function has significant implications for stem cell biology, repair of lung injuries, and diseases such as cancer.
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Details
- Title
- Dynamic changes in intracellular ROS levels regulate airway basal stem cell homeostasis through Nrf2-dependent Notch signaling
- Creators
- Manash K Paul - Department of Pediatrics, Mattel Children's Hospital, University of California, Los Angeles, Los Angeles, CA 90095, USABharti Bisht - Department of Pediatrics, Mattel Children's Hospital, University of California, Los Angeles, Los Angeles, CA 90095, USADaphne O Darmawan - Department of Pediatrics, Mattel Children's Hospital, University of California, Los Angeles, Los Angeles, CA 90095, USARichard Chiou - Department of Pediatrics, Mattel Children's Hospital, University of California, Los Angeles, Los Angeles, CA 90095, USAVi L Ha - Department of Pediatrics, Mattel Children's Hospital, University of California, Los Angeles, Los Angeles, CA 90095, USAWilliam D Wallace - Department of Pathology, University of California, Los Angeles, Los Angeles, CA 90095, USAAndrew T Chon - Department of Pediatrics, Mattel Children's Hospital, University of California, Los Angeles, Los Angeles, CA 90095, USAAhmed E Hegab - Keio UniversityTristan Grogan - Department of Biostatistics, University of California, Los Angeles, Los Angeles, CA 90095, USADavid A ElashoffJackelyn A Alva-Ornelas - Department of Pediatrics, Mattel Children's Hospital, University of California, Los Angeles, Los Angeles, CA 90095, USABrigitte N Gomperts
- Publication Details
- Cell stem cell, v 15(2), pp 199-214
- Publisher
- Elsevier
- Grant note
- HL094561 / NHLBI NIH HHS R01 HL094561 / NHLBI NIH HHS P30 CA016042 / NCI NIH HHS UL1 TR000124 / NCATS NIH HHS UL1TR000124 / NCATS NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Engineering Technology
- Web of Science ID
- WOS:000340880100012
- Scopus ID
- 2-s2.0-84905905334
- Other Identifier
- 991020547612604721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Cell & Tissue Engineering
- Cell Biology