Format

Send to

Choose Destination
Stem Cell Reports. 2018 Feb 13;10(2):600-614. doi: 10.1016/j.stemcr.2017.12.007. Epub 2018 Jan 4.

Real-Time Monitoring of Glutathione in Living Cells Reveals that High Glutathione Levels Are Required to Maintain Stem Cell Function.

Author information

1
Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea; Institute of Human-Environment Interface Biology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.
2
Department of Chemistry, Korea University, Seoul 02841, Republic of Korea.
3
Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea; Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea.
4
Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.
5
Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea.
6
Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea. Electronic address: d0shin03@amc.seoul.kr.
7
Department of Chemistry, Korea University, Seoul 02841, Republic of Korea. Electronic address: kchoi@korea.ac.kr.
8
Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea; Institute of Human-Environment Interface Biology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea. Electronic address: igkim@plaza.snu.ac.kr.

Abstract

The core functions of stem cells (SCs) are critically regulated by their cellular redox status. Glutathione is the most abundant non-protein thiol functioning as an antioxidant and a redox regulator. However, an investigation into the relationship between glutathione-mediated redox capacity and SC activities is hindered by lack of probe. Here, we demonstrate that cyanoacrylamide-based coumarin derivatives are ratiometric probes suitable for the real-time monitoring of glutathione levels in living SCs. These probes revealed that glutathione levels are heterogeneous among subcellular organelles and among individual cells and show dynamic changes and heterogeneity in repopulating SCs depending on oxidative stress or culture conditions. Importantly, a subpopulation of SCs with high glutathione levels exhibited increased stemness and migration activities in vitro and showed improved therapeutic efficiency in treating asthma. Our results indicate that high glutathione levels are required for maintaining SC functions, and monitoring glutathione dynamics and heterogeneity can advance our understanding of the cellular responses to oxidative stress.

KEYWORDS:

asthma; fluorescent probe; glutathione; heterogeneity; migration; oxidative stress; pluripotency; real-time monitoring; self-renewal; stem cell

PMID:
29307581
PMCID:
PMC5830891
DOI:
10.1016/j.stemcr.2017.12.007
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center