HSC-derived fatty acid oxidation in steady-state and stressed hematopoiesis

Mistry, Jayna J; Bowles, Kristian M.; Rushworth, Stuart A.

doi:10.1016/j.exphem.2022.10.003

Cited by 6 publications

(2 citation statements)

References 97 publications

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“…Maintenance of HSC homeostasis and in deciding differentiation fate during nutrient deprivation, metabolic regulation definitely plays a center role to compensate for the lack of energy source and help cellular adaptation (Nakamura-Ishizu et al, 2020;Mistry et al, 2022). Strikingly, we found that metabolic pathways are sharply shifted from mitochondria to the cytoplasm (Fig.…”

Section: Discussionmentioning

confidence: 76%

Metabolic regulation in erythroid differentiation by systemic ketogenesis in fasted mice

Ma,

Arima,

Umemoto

et al. 2024

Experimental Hematology

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Section: Discussionmentioning

confidence: 76%

Metabolic regulation in erythroid differentiation by systemic ketogenesis in fasted mice

Ma,

Arima,

Umemoto

et al. 2024

Experimental Hematology

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“…Consequently, during homeostasis, almost the entire HSC compartment (~ 90%) resides in the resting phase, G0 (Cheshier et al , 1999 ; Zhang et al , 2022b ), while the downstream multipotent progenitors are actively cycling to maintain daily turnover (Sun et al , 2014 ; Busch et al , 2015 ; Sawai et al , 2016 ). HSC quiescence is associated with glycolytic energy production rather than oxidative phosphorylation (OXPHOS), ensuring low reactive oxygen species (ROS) production, which can be harmful to the genomic integrity (Ludin et al , 2014 ; Mistry et al , 2023 ) (Box 1 ; Fig 1A ). Additionally, low levels of metabolic activators and protein synthesis are hallmarks of quiescent HSCs (Chen et al , 2008 ; Gan et al , 2008 ; Signer et al , 2014 ; Ito et al , 2016 ; Scognamiglio et al , 2016 ; Vannini et al , 2016 ; Cabezas‐Wallscheid et al , 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Bidirectional interplay between metabolism and epigenetics in hematopoietic stem cells and leukemia

Zhang,

Schönberger,

Cabezas‐Wallscheid

2023

The EMBO Journal

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During the last decades, remarkable progress has been made in further understanding the complex molecular regulatory networks that maintain hematopoietic stem cell (HSC) function. Cellular and organismal metabolisms have been shown to directly instruct epigenetic alterations, and thereby dictate stem cell fate, in the bone marrow. Epigenetic regulatory enzymes are dependent on the availability of metabolites to facilitate DNA‐ and histone‐modifying reactions. The metabolic and epigenetic features of HSCs and their downstream progenitors can be significantly altered by environmental perturbations, dietary habits, and hematological diseases. Therefore, understanding metabolic and epigenetic mechanisms that regulate healthy HSCs can contribute to the discovery of novel metabolic therapeutic targets that specifically eliminate leukemia stem cells while sparing healthy HSCs. Here, we provide an in‐depth review of the metabolic and epigenetic interplay regulating hematopoietic stem cell fate. We discuss the influence of metabolic stress stimuli, as well as alterations occurring during leukemic development. Additionally, we highlight recent therapeutic advancements toward eradicating acute myeloid leukemia cells by intervening in metabolic and epigenetic pathways.

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