Reactive oxygen species prime Drosophila haematopoietic progenitors for differentiation
Open accessAbstract
Reactive oxygen species (ROS), produced during various electron transfer reactions in vivo, are generally considered to be deleterious to cells. In the mammalian haematopoietic system, haematopoietic stem cells contain low levels of ROS. However, unexpectedly, the common myeloid progenitors (CMPs) produce significantly increased levels of ROS(2). The functional significance of this difference in ROS level in the two progenitor types remains unresolved. Here we show that Drosophila multipotent haematopoietic progenitors, which are largely akin to the mammalian myeloid progenitors, display increased levels of ROS under in vivo physiological conditions, which are downregulated on differentiation. Scavenging the ROS from these haematopoietic progenitors by using in vivo genetic tools retards their differentiation into mature blood cells. Conversely, increasing the haematopoietic progenitor ROS beyond their basal level triggers precocious differentiation into all three mature blood cell types found in Drosophila, through a signalling pathway that involves JNK and FoxO activation as well as Polycomb downregulation. We conclude that the developmentally regulated, moderately high ROS level in the progenitor population sensitizes them to differentiation, and establishes a signalling role for ROS in the regulation of haematopoietic cell fate. Our results lead to a model that could be extended to reveal a probable signalling role for ROS in the differentiation of CMPs in mammalian haematopoietic development and oxidative stress response.
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In Drosophila, hematopoietic stem and progenitor cell differentiation is regulated by physiological ROS signaling.
“in Drosophila, hematopoietic stem and progenitor cell differentiation is regulated by physiological ROS signaling26.”
From Stem cell aging: mechanisms, regulators and therapeutic opportunities (2014) · cites this paper as [26]
In Drosophila melanogaster, ROS levels increase as multipotent hematopoietic progenitors differentiate.
“ROS levels increase as Drosophila multipotent hematopoietic progenitors differentiate 47”
From Mitochondrial reactive oxygen species regulate cellular signaling and dictate biological outcomes (2010) · cites this paper as [47]
Overproduction of mitochondrial ROS leads to precocious differentiation into mature blood cells, whereas increased scavenging ability inhibits differentiation.
“overproduction of mitochondrial ROS leads to precocious differentiation into mature blood cells whereas increased scavenging ability inhibits differentiation.”
From Mitochondrial reactive oxygen species regulate cellular signaling and dictate biological outcomes (2010) · cites this paper as [47]
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- Authors
- Owusu-Ansah, E., & Banerjee, U.
- Affiliations
- University of California, Los Angeles (US)
- Corresponding author
- Banerjee, Utpal
- Venue
- Nature
- Published
- 2009-09
- Volume
- 461
- Issue
- 7263
- Pages
- 537-541
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC4380287
- OpenAlex
- W2002426440
- Cited by
- 742
- References
- 26
- Citations by year
- 2026: 13 · 2025: 21 · 2024: 43 · 2023: 36 · 2022: 32 · 2021: 46 · 2020: 35 · 2019: 48 · 2018: 54 · 2017: 50 · 2016: 58 · 2015: 46 · 2014: 64 · 2013: 62 · 2012: 44
- FWCI
- 17.96
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (T32HL069766, R01HL067395)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (F32AR057291)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Immunology and Microbiology › Immunology › Invertebrate Immune Response Mechanisms
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Keywords
- reactive oxygen species, hematopoietic progenitor cells, common myeloid progenitors, hematopoietic differentiation, cell fate regulation, JNK signaling, FOXO, Polycomb, reactive oxygen species scavenging, hematopoietic stem cells, blood cell types
- MeSH terms
- Animals, Blood Cells, Cell Differentiation, Drosophila melanogaster, Hematopoiesis, Hematopoietic Stem Cells, Larva, Lymphoid Tissue, Phenotype, Signal Transduction, Down-Regulation, Reactive Oxygen Species, Oxidative Stress, Drosophila Proteins, Multipotent Stem Cells, JNK Mitogen-Activated Protein Kinases, Forkhead Transcription Factors, Polycomb Repressive Complex 1
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