Reactive Oxygen Species prime Drosophila haematopoietic progenitors for differentiation

By Edward Owusu-Ansah, U. Banerjee. Nature, 2009

727 citations recorded by the source corpus.

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 ROS2. 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.

Subfields: Cell Biology, Immunology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/10b548b962c7f091b33d20db4f7c2cbe7b363dff

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Citations in the corpus

CD44 variant regulates redox status in cancer cells by stabilizing the xCT subunit of system xc(-) and thereby promotes tumor growth. (2011, background): “, 2006) and that, in Drosophila, high ROS levels sensitize hematopoietic progenitors to the induction of differentiation (Owusu-Ansah and Banerjee, 2009).”
Role of nrf2 in oxidative stress and toxicity. (2013, background): “Several types of stem and progenitor cells exhibit low intracellular concentrations of ROS that may serve as a critical condition for stemness and pluripotency; on the other hand, a rise in ROS appears to be required for proper differentiation of myeloid progenitor cells (120).”
Polycomb group proteins: multi-faceted regulators of somatic stem cells and cancer. (2010, unknown): “Accumulating evidence indicates that oxidative metabolism plays a crucial role in maintaining the self-renewal properties of somatic stem cells and that accumulation of high ROS levels leads to premature differentiation (Jang and Sharkis, 2007; Owusu-Ansah and Banerjee, 2009).”
The Oxygen Rich Postnatal Environment Induces Cardiomyocyte Cell Cycle Arrest Through DNA Damage Response (2014, unknown): “…continued on next page) 568 Cell 157, 565–579, April 24, 2014 ª2014 Elsevier Inc. zebrafish heart and the early neonatal mouse heart and outline the time frame of the metabolic switch from anaerobic glycolysis tomitochondrial oxidative phosphorylation inmouse heart within one week after birth.”
Transcriptional regulation of ROS controls transition from proliferation to differentiation in the root. (2010, background): “Drosophila, changing ROS levels can switch the status of hematopoietic cells from proliferation to differentiation (Owusu-Ansah and Banerjee, 2009).”
ROS Function in Redox Signaling and Oxidative Stress (2014, background): “Similarly, in Drosophila hematopoietic progenitors, increasing ROS triggers differentiation, whereas decreasing ROS impairs differentiation [141].”
Redox regulation of FoxO transcription factors (2015, result): “These results are in line with a number of studies showing that differentiation factors induce a transient increase in ROS levels in the target cells [296].”
Metabolic Plasticity in Stem Cell Homeostasis and Differentiation (2012, unknown): “Indeed, antioxidant treatment impairs the ability of MSCs and HSCs to undergo differentiation (Owusu-Ansah and Banerjee, 2009; Tormos et al., 2011); however, the targets of ROS in differentiation programs remain unknown.”
Metabolic regulation of hematopoietic stem cells in the hypoxic niche. (2011, background): “A recent study in Drosophila concluded that ROS prime hematopoietic progenitors were a population similar to mammalian myeloid progenitor cells in terms of differentiation, suggesting that ROS functions as a differentiation factor in this context (Owusu-Ansah and Banerjee, 2009).”
The autophagy protein Atg7 is essential for hematopoietic stem cell maintenance (2011, background): “, 2002): (a) the cells infiltrating nonhematopoietic and hematopoietic organs are atypical and blast-like, (b) most animals had >20% myeloid blasts in the BM, and (c) the myeloproliferation can be transplanted to recipients of ROS above their basal levels triggers precocious differentiation (Owusu-A”