Dynamic Changes in Intracellular ROS Levels Regulate Airway Basal Stem Cell Homeostasis through Nrf2-Dependent Notch Signaling

被引：222

作者：

Paul, Manash K. ^{[1
]}

Bisht, Bharti ^{[1
]}

Darmawan, Daphne O. ^{[1
]}

Chiou, Richard ^{[1
]}

Ha, Vi L. ^{[1
]}

Wallace, William D. ^{[2
]}

Chon, Andrew T. ^{[1
]}

Hegab, Ahmed E. ^{[3
]}

Grogan, Tristan ^{[4
]}

Elashoff, David A. ^{[4
,5
]}

Alva-Ornelas, Jackelyn A. ^{[1
]}

Gomperts, Brigitte N. ^{[1
,5
,6
,7
]}

机构：

[1] Univ Calif Los Angeles, Dept Pediat, Mattel Childrens Hosp, Los Angeles, CA 90095 USA

[2] Univ Calif Los Angeles, Dept Pathol, Los Angeles, CA 90095 USA

[3] Keio Univ, Sch Med, Dept Med, Div Pulm Med, Tokyo 1608582, Japan

[4] Univ Calif Los Angeles, Dept Biostat, Los Angeles, CA 90095 USA

[5] Univ Calif Los Angeles, Los Angeles, CA 90095 USA

[6] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA

[7] Univ Calif Los Angeles, Eli & Edythe Broad Stem Cell Res Ctr, Los Angeles, CA 90095 USA

来源：

CELL STEM CELL | 2014年 / 15卷 / 02期

关键词：

SELF-RENEWAL; NRF2; ACTIVATION; PATHWAY; CANCER; MAINTENANCE; ROLES; PROLIFERATION; MECHANISMS; STRESS;

D O I：

10.1016/j.stem.2014.05.009

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

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.

引用

页码：199 / 214

页数：16

共 48 条

[1] Cigarette Smoke-induced Oxidative Stress A Role in Chronic Obstructive Pulmonary Disease Skeletal Muscle Dysfunction
Barreiro, Esther
Peinado, Victor I.
Galdiz, Juan B.
Ferrer, Elisabet
Mann-Corral, Judith
Sanchez, Francisco
Gea, Joaquim
Albert Barbera, Joan
[J]. AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2010, 182 (04) : 477 - 488
[2] Canonical Notch signaling functions as a commitment switch in the epidermal lineage
Blanpain, Cedric
Lowry, William E.
Pasolli, H. Amalia
Fuchs, Elaine
[J]. GENES & DEVELOPMENT, 2006, 20 (21) : 3022 - 3035
[3] Evidence for stem-cell niches in the tracheal epithelium
Borthwick, DW
Shahbazian, M
Krantz, QT
Dorin, JR
Randell, SH
[J]. AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 2001, 24 (06) : 662 - 670
[4] Prdm16 promotes stem cell maintenance in multiple tissues, partly by regulating oxidative stress
Chuikov, Sergei
Levi, Boaz P.
Smith, Michael L.
Morrison, Sean J.
[J]. NATURE CELL BIOLOGY, 2010, 12 (10) : 999 - 1006
[5] Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis
De Nicola, Gina M.
Karreth, Florian A.
Humpton, Timothy J.
Gopinathan, Aarthi
Wei, Cong
Frese, Kristopher
Mangal, Dipti
Yu, Kenneth H.
Yeo, Charles J.
Calhoun, Eric S.
Scrimieri, Francesca
Winter, Jordan M.
Hruban, Ralph H.
Iacobuzio-Donahue, Christine
Kern, Scott E.
Blair, Ian A.
Tuveson, David A.
[J]. NATURE, 2011, 475 (7354) : 106 - U128
[6] Evidence for multiple roles for grainyheadlike 2 in the establishment and maintenance of human mucociliary airway epithelium
Gao, Xia
Vockley, Christopher M.
Pauli, Florencia
Newberry, Kimberly M.
Xue, Yan
Randell, Scott H.
Reddy, Timothy E.
Hogan, Brigid L. M.
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2013, 110 (23) : 9356 - 9361
[7] Human Tracheobronchial Basal Cells Normal versus Remodeling/Repairing Phenotypes In Vivo and In Vitro
Ghosh, Moumita
Ahmad, Shama
Jian, Abhilasha
Li, Bilan
Smith, Russell W.
Helm, Karen M.
Seibold, Max A.
Groshong, Steven D.
White, Carl W.
Reynolds, Susan D.
[J]. AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 2013, 49 (06) : 1127 - 1134
[8] Notch signaling promotes airway mucous metaplasia and inhibits alveolar development
Guseh, J. Sawalla
Bores, Sam A.
Stanger, Ben Z.
Zhou, Qiao
Anderson, William J.
Melton, Douglas A.
Rajagopal, Jayaraj
[J]. DEVELOPMENT, 2009, 136 (10): : 1751 - 1759
[9] Comprehensive genomic characterization of squamous cell lung cancers
Hammerman, Peter S.
Lawrence, Michael S.
Voet, Douglas
Jing, Rui
Cibulskis, Kristian
Sivachenko, Andrey
Stojanov, Petar
McKenna, Aaron
Lander, Eric S.
Gabriel, Stacey
Getz, Gad
Sougnez, Carrie
Imielinski, Marcin
Helman, Elena
Hernandez, Bryan
Pho, Nam H.
Meyerson, Matthew
Chu, Andy
Chun, Hye-Jung E.
Mungall, Andrew J.
Pleasance, Erin
Robertson, A. Gordon
Sipahimalani, Payal
Stoll, Dominik
Balasundaram, Miruna
Birol, Inanc
Butterfield, Yaron S. N.
Chuah, Eric
Coope, Robin J. N.
Corbett, Richard
Dhalla, Noreen
Guin, Ranabir
Hirst, Anhe Carrie
Hirst, Martin
Holt, Robert A.
Lee, Darlene
Li, Haiyan I.
Mayo, Michael
Moore, Richard A.
Mungall, Karen
Nip, Ka Ming
Olshen, Adam
Schein, Jacqueline E.
Slobodan, Jared R.
Tam, Angela
Thiessen, Nina
Varhol, Richard
Zeng, Thomas
Zhao, Yongjun
Jones, Steven J. M.
[J]. NATURE, 2012, 489 (7417) : 519 - 525
[10] Mechanisms of Stem Cell Self-Renewal
He, Shenghui
Nakada, Daisuke
Morrison, Sean J.
[J]. ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY, 2009, 25 : 377 - 406

← 1 2 3 4 5 →