Hand of FATe: lipid metabolism in hematopoietic stem cells

Lee, Man K.S.; Al-Sharea, Annas; Dragoljevic, Dragana; Murphy, Andrew

doi:10.1097/mol.0000000000000500

Cited by 18 publications

(2 citation statements)

References 54 publications

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“…Lipids are a vast class of biomolecules which fulfill three general functions: energy, membrane structure, and signaling. 4, 5 To date, an impressive amount of experimental data has given insights into membrane biogenesis as well as homeostasis and lipid-protein interactions, which paves the way for targeted modification of membrane lipid compositions. 23 In 1987, Dio et al showed that adding SFAs (palmitic acid, etc.)…”

Section: Discussionmentioning

confidence: 99%

“…1 In addition, recent studies have demonstrated a role for lipids in cell fate decisions during hematopoiesis. [2][3][4][5] Cells obtain lipids in several ways; essential fatty acids are taken up from the diet (mostly polyunsaturated fatty acids (PUFAs, containing multiple double bonds), while saturated fatty acids (SFAs, no double bonds) can be produced via de novo lipogenesis. 6 As such, how lipids are produced and incorporated into cells can be regulated through cellular metabolism and dietary intervention.…”

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confidence: 99%

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Efficient megakaryopoiesis and platelet production require phospholipid remodeling and PUFA uptake through CD36

Barrachina

Pernes

Becker

et al. 2023

Preprint

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Lipids contribute to hematopoiesis and membrane properties and dynamics, however, little is known about the role of lipids in megakaryopoiesis. Here, a lipidomic analysis of megakaryocyte progenitors, megakaryocytes, and platelets revealed a unique lipidome progressively enriched in polyunsaturated fatty acid (PUFA)-containing phospholipids. In vitro, inhibition of both exogenous fatty acid functionalization and uptake and de novo lipogenesis impaired megakaryocyte differentiation and proplatelet production. In vivo, mice on a high saturated fatty acid diet had significantly lower platelet counts, which was prevented by eating a PUFA-enriched diet. Fatty acid uptake was largely dependent on CD36, and its deletion in mice resulted in thrombocytopenia. Moreover, patients with a CD36 loss-of-function mutation exhibited thrombocytopenia and increased bleeding. Our results suggest that fatty acid uptake and regulation is essential for megakaryocyte maturation and platelet production, and that changes in dietary fatty acids may be a novel and viable target to modulate platelet counts.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Efficient megakaryopoiesis and platelet production require phospholipid remodeling and PUFA uptake through CD36

Barrachina

Pernes

Becker

et al. 2023

Preprint

View full text Add to dashboard Cite

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Fat for fuel: lipid metabolism in haematopoiesis

et al. 2019

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The importance of metabolic regulation in the immune system has launched back into the limelight in recent years. Various metabolic pathways have been examined in the context of their contribution to maintaining immune cell homeostasis and function. Moreover, this regulation is also important in the immune cell precursors, where metabolism controls their maintenance and cell fate. This review will discuss lipid metabolism in the context of haematopoiesis, that is blood cell development. We specifically focus on nonoxidative lipid metabolism which encapsulates the synthesis and degradation of the major lipid classes such as phospholipids, sphingolipids and sterols. We will also discuss how these metabolic processes are affected by haematological malignancies such as leukaemia and lymphoma, which are known to have altered metabolism, and how these different pathways contribute to the pathology.

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