A low level of reactive oxygen species selects for primitive hematopoietic stem cells that may reside in the low-oxygenic niche
Open accessAbstract
A low-oxygenic niche in bone marrow limits reactive oxygen species (ROS) production, thus providing long-term protection for hematopoietic stem cells (HSCs) from ROS stress. Although many approaches have been used to enrich HSCs, none has been designed to isolate primitive HSCs located within the low-oxygenic niche due to difficulties of direct physical access. Here we show that an early HSC population that might reside in the niche can be functionally isolated by taking advantage of the relative intracellular ROS activity. Many attributes of primitive HSCs in the low-oxygenic osteoblastic niche, such as quiescence, and calcium receptor, N-cadherin, Notch1, and p21 are higher in the ROSlow population. Intriguingly, the ROSlow population has a higher self-renewal potential. In contrast, significant HSC exhaustion in the ROShigh population was observed following serial transplantation, and expression of activated p38 mitogen-activated protein kinase (MAPK) and mammalian target of rapamycin (mTOR) was higher in this population. Importantly, treatment with an antioxidant, a p38 inhibitor, or rapamycin was able to restore HSC function in the ROShigh population. Thus, more potent HSCs associated with the low-oxygenic niche can be isolated by selecting for the low level of ROS expression. The ROS-related signaling pathways together with specific characteristics of niche HSCs may serve as targets for beneficial therapies.
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In mice, the frequency of hematopoietic stem cells with low ROS levels declines with age.
“the frequency of blood-forming hematopoietic stem cells (HSCs) with low ROS levels declines with age in mice10”
From Stem cell aging: mechanisms, regulators and therapeutic opportunities (2014) · cites this paper as [10]
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- Authors
- Jang, Y.-Y., & Sharkis, S. J.
- Affiliations
- Johns Hopkins University (US)
- ORCID
- Jang, Yoon-Young
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2007-10-15
- Volume
- 110
- Issue
- 8
- Pages
- 3056-3063
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- PMC
- PMC2018677
- OpenAlex
- W2135470678
- Cited by
- 894
- References
- 49
- Citations by year
- 2026: 14 · 2025: 34 · 2024: 40 · 2023: 42 · 2022: 38 · 2021: 62 · 2020: 45 · 2019: 57 · 2018: 58 · 2017: 46 · 2016: 47 · 2015: 75 · 2014: 57 · 2013: 74 · 2012: 53
- FWCI
- 21.14
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Blood (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Johns Hopkins University
- National Institutes of Health
- National Heart, Lung, and Blood Institute (R01HL054330)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK070971)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- hematopoietic stem cells, reactive oxygen species, bone marrow microenvironment, HSC isolation, HSC quiescence, HSC self-renewal, HSC exhaustion, p38 MAPK, mTOR, antioxidant therapy, rapamycin, Notch1, N-cadherin, p21, osteoblastic niche
- MeSH terms
- Animals, Cell Adhesion, Cell Differentiation, Cytological Techniques, Female, Flow Cytometry, Fluoresceins, Hematopoiesis, Hematopoietic Stem Cells, Male, Oxygen, Protein Kinases, Blotting, Western, Bone Marrow Transplantation, Polymerase Chain Reaction, Reactive Oxygen Species, Hematopoietic Stem Cell Transplantation, p38 Mitogen-Activated Protein Kinases, Mice, TOR Serine-Threonine Kinases
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