Mitochondrial gene knockout HL60ρ0 cells show preferential differentiation into monocytes/macrophages

Herst, Patries M.; Levine, D.; Berridge, Michael V.

doi:10.1016/j.leukres.2005.03.013

Cited by 10 publications

(6 citation statements)

References 30 publications

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“…High mitochondrial dependency was observed during neutrophil, but not macrophage differentiation. Consistent with these observations, a previous report demonstrated that HL-60ρ0 cells, in which mitochondria are depleted and only glycolysis is the ATP source, could differentiate into macrophages but not neutrophils [27]. These findings indicated that ATP for ER stress/UPR, especially XBP1 activation, is mainly supplied from mitochondria for neutrophil differentiation, whereas glycolysis-derived ATP is sufficient for macrophage differentiation (Fig.…”

Section: Importance Of Atp Supply From Glycolysis and Mitochondrial Osupporting

confidence: 87%

Mitochondrial Activity and Unfolded Protein Response are Required for Neutrophil Differentiation

Tanimura

Miyoshi

Horiguchi

et al. 2018

Cell Physiol Biochem

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Background/Aims: Endoplasmic reticulum (ER) stress and unfolded protein response (UPR) are involved in hematopoietic differentiation. However, the mechanistic linkage between ER stress/UPR and hematopoietic differentiation remains unclear. Methods: We used bipotent HL-60 cells as an in vitro hematopoietic differentiation system to investigate the role of ER stress and UPR activity in neutrophil and macrophage differentiation. Results: The in vitro differentiation analysis revealed that ER stress decreased during both neutrophil and macrophage differentiations, and the activities of PERK and ATF6 were decreased and that of IRE1α was increased during neutrophil differentiation in a stage-specific manner. By contrast, the activities of ATF6 and ATF4 decreased during macrophage differentiation. When the cells were treated with oligomycin, the expression of CD11b, a myelocytic differentiation marker, and morphological differentiation were suppressed, and XBP-1 activation was inhibited during neutrophil differentiation, whereas CD11b expression was maintained, and morphological differentiation was not obviously affected during macrophage differentiation. Conclusion: In this study, we demonstrated that neutrophil differentiation is regulated by ER stress/UPR that is supported by mitochondrial ATP supply, in which IRE1α-XBP1 activation is essential. Our findings provide the evidence that mitochondrial energy metabolism may play a critical role in neutrophil differentiation.

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Section: Importance Of Atp Supply From Glycolysis and Mitochondrial Osupporting

confidence: 87%

Mitochondrial Activity and Unfolded Protein Response are Required for Neutrophil Differentiation

Tanimura

Miyoshi

Horiguchi

et al. 2018

Cell Physiol Biochem

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“…In HIGH OXPHOS AML (MOLM14) cells, we tested pharmacological agents well known to inhibit OXPHOS activities through the inhibition of mitochondrial protein synthesis (Tigecycline, TIG (40); Ethidium Bromide, (36,41)), Electron Transport Chain complex I (ETCI; Phenformin or Metformin (42); Rotenone) or Electron Transport Chain complex III (ETCIII; antimycin A or atovaquone (43)). As expected and shown by Bozhena Jhas et al (44), TIG-treated HIGH OXPHOS MOLM14 cells (Fig.…”

Section: Resultsmentioning

confidence: 99%

Chemotherapy-Resistant Human Acute Myeloid Leukemia Cells Are Not Enriched for Leukemic Stem Cells but Require Oxidative Metabolism

et al. 2017

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Chemotherapy-resistant human acute myeloid leukemia (AML) cells are thought to be enriched in quiescent immature leukemic stem cells (LSCs). To validate this hypothesis in vivo, we developed a clinically relevant chemotherapeutic approach treating patient-derived xenograft (PDX) with cytarabine. Cytarabine residual AML cells are enriched neither in immature, quiescent cells nor LSCs. Strikingly, cytarabine-resistant pre-existing and persisting cells displayed high levels of reactive oxygen species, showed increased mitochondrial mass, and retained active polarized mitochondria, consistent with a high oxidative phosphorylation (OXPHOS) status. Cytarabine residual cells exhibited increased fatty acid oxidation, upregulated CD36 expression and a HIGH OXPHOS gene signature predictive for treatment response in PDX and AML patients. HIGH OXPHOS but not LOW OXPHOS human AML cell lines were chemoresistant in vivo. Targeting mitochondrial protein synthesis, electron transfer, or fatty acid oxidation induced an energetic shift towards LOW OXPHOS and markedly enhanced anti-leukemic effects of cytarabine. Together, this study demonstrates that essential mitochondrial functions contribute to cytarabine resistance in AML and are a robust hallmark of cytarabine sensitivity and a promising therapeutic avenue to treat AML residual disease.

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“…HL-60 cells, isolated in 1976 from a patient with acute myeloblastic leukemia with maturation, FAB-M2, , have often been used as an in vitro model to study the differentiation and signal transduction. , Their lineage can be affected by a number of readily available chemicals, including dimethyl sulfoxide (DMSO), , which pushes the cells toward a granulocytic lineage. DMSO-induced HL-60 differentiation, which is characterized by decreased size and decreased nuclear/cytoplasm ratio, has been characterized previously using optical methods and thus was a promising comparison as an initial application.…”

Section: Resultsmentioning

confidence: 99%

Toward Label-Free Optical Fractionation of Blood—Optical Force Measurements of Blood Cells

2011

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There is a compelling need to develop systems capable of processing blood and other particle streams for detection of pathogens that are sensitive, selective, automated, and cost/size effective. Our research seeks to develop laser-based separations that do not rely on prior knowledge, antibodies, or fluorescent molecules for pathogen detection. Rather, we aim to harness inherent differences in optical pressure, which arise from variations in particle size, shape, refractive index, or morphology, as a means of separating and characterizing particles. Our method for measuring optical pressure involves focusing a laser into a fluid flowing opposite to the direction of laser propagation. As microscopic particles in the flow path encounter the beam, they are trapped axially along the beam and are pushed upstream from the laser focal point to rest at a point where the optical and fluid forces on the particle balance. On the basis of the flow rate at which this balance occurs, the optical pressure felt by the particle can be calculated. As a first step in the development of a label-free device for processing blood, a system has been developed to measure optical pressure differences between the components of human blood, including erythrocytes, monocytes, granulocytes, and lymphocytes. Force differentials have been measured between various components, indicating the potential for laser-based separation of blood components based upon differences in optical pressure. Potential future applications include the early detection of blood-borne pathogens for the prevention of sepsis and other diseases as well as the detection of biological threat agents.

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Mitochondrial gene knockout HL60ρ0 cells show preferential differentiation into monocytes/macrophages

Cited by 10 publications

References 30 publications

Mitochondrial Activity and Unfolded Protein Response are Required for Neutrophil Differentiation

Mitochondrial Activity and Unfolded Protein Response are Required for Neutrophil Differentiation

Chemotherapy-Resistant Human Acute Myeloid Leukemia Cells Are Not Enriched for Leukemic Stem Cells but Require Oxidative Metabolism

Toward Label-Free Optical Fractionation of Blood—Optical Force Measurements of Blood Cells

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