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Transcriptome changes accompany mitochondrial membrane potential heterogeneity in mouse embryonic and induced pluripotent stem cells

ABSTRACT: Transcriptome changes accompany mitochondrial membrane potential heterogeneity in mouse embryonic and induced pluripotent stem cells

PROVIDER: PRJNA528823 | ENA |

REPOSITORIES: ENA

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Transcriptome changes accompany mitochondrial membrane potential heterogeneity in mouse embryonic and induced pluripotent stem cells

Project description:Stem cells are uniquely dependent on both oxidative phosphorylation and glycolysis to maintain pluripotency and drive differentiation. Here, we identified that stem cells sorted by their inherent differences in mitochondrial activity exhibited significantly altered germline differentiation potential. Stem cells with lower average mitochondrial membrane potential were less proliferative and generated less ROS and ATP despite having a similar mitochondrial DNA copy number as cells with higher membrane potential. We demonstrate that pluripotent stem cells exhibit a large range of mitochondrial activity from an otherwise homogenous population, and that they are dependent on this activity to drive differentiation.

2020-03-22 | GSE128769 | GEO

Targeting Mitochondrial Membrane Potential as A Generalized Strategy to Eradicate Leukemic Stem Cells

Project description:Heterogeneity in acute myeloid leukemias makes the development of effective therapies challenging. In the current study, we found that mitochondrial membrane potential (MMP) differs as a function of metabolism and stemness of leukemic cells. Mechanistically, MMP is regulated by mitochondrial translation, whose rate is sensitive to the availability of asparagine. Interestingly, this MMP-modulating mechanism is hijacked by leukemic cells, especially leukemic stem cells (LSCs), to elevated MMP to evade chemotherapy and thus depletion of asparagine by asparaginase chemo-sensitizes LSCs. To further evaluate the function of MMP-modulating mechanisms in disease development and drug resistance, we performed a targeted drug screen and identified Alexidine as a strong MMP-lowering agent via repressing mitochondrial translation. We revealed that Alexidine binds to cardiolipin to interfere with the inner membrane localization of mitochondrial ribosomes to inhibit mitochondrial translation. We demonstrated that Alexidine has anti-leukemic effect and is a potent chemo-sensitizer. Together, our study suggests that targeting MMP-modulating machineries is a promising approach to eradicate leukemic cells.

2024-09-01 | GSE266913 | GEO

OXPHOS deficiency activates global adaptation pathways to maintain mitochondrial membrane potential

Project description:Reduction of mitochondrial membrane potential is a hallmark of mitochondrial dysfunction. It activates adaptive responses in organisms from yeast to human to rewire metabolism, remove depolarized mitochondria, and degrade unimported precursor proteins. It remains unclear how cells maintain mitochondrial membrane potential, which is critical for maintaining iron-sulfur cluster (ISC) synthesis, an indispensable function of mitochondria. Here we show that yeast oxidative phosphorylation mutants deficient in complex III, IV, V, and mtDNA respectively, have graded reduction of mitochondrial membrane potential and proliferation rates. Extensive omics analyses of these mutants show that accompanying mitochondrial membrane potential reduction, these mutants progressively activate adaptive responses, including transcriptional downregulation of ATP synthase inhibitor Inh1 and OXPHOS subunits, Puf3-mediated upregulation of import receptor Mia40 and global mitochondrial biogenesis, Snf1/AMPK-mediated upregulation of glycolysis and repression of ribosome biogenesis, and transcriptional upregulation of cytoplasmic chaperones. These adaptations disinhibit mitochondrial ATP hydrolysis, remodel mitochondrial proteome, and optimize ATP supply to mitochondria to convergently maintain mitochondrial membrane potential, ISC biosynthesis, and cell proliferation.

2020-11-27 | GSE162197 | GEO

Cell cycle positioning drives heterogeneity within the pluripotent stem cell compartment

Project description:Heterogeneity in pluripotent cells marks a metastable state where cells may drift between native and lineage-primed populations. While the role for these heterogeneities are unclear, they may reflect the dynamic equilibriums of signaling networks and have a direct effect on differentiation potentialities. Here, we report the role of the cell cycle in establishing heterogeneity of human pluripotent stem cells. By utilizing the FUCCI cell cycle indicator system coupled to fluorescent activated cell sorting (FACS), we have uncovered that the cell cycle drives heterogeneity at the epigenetic, transcriptional and post-transcriptional levels. Our data show widespread dynamics in 5-hydroxymethylcytosine (5hmC) during the cell cycle. Furthermore, transcript profiling by RNA-sequencing identified >500 genes that were cell cycle-regulated, of which the largest cohort of genes were transcriptional regulators. In sum, we demonstrate the role of the cell cycle in coordinating cellular transitions between metastable states in pluripotent stem cells. mRNA sequencing of the cell cycle phases; early & late G1, S and G2/S from human ES cells in triplicate.

2013-12-19 | E-GEOD-53481 | biostudies-arrayexpress

Cell cycle positioning drives heterogeneity within the pluripotent stem cell compartment

2013-12-19 | GSE53481 | GEO

Astrocyte alterations that accompany neuroinflammation induced anhedonia

Project description:Astrocyte alterations that accompany neuroinflammation induced anhedonia

| PRJNA557455 | ENA

Landscape of Prostate-Specific Membrane Antigen Heterogeneity in Metastatic Prostate Cancer II

Project description:Landscape of Prostate-Specific Membrane Antigen Heterogeneity in Metastatic Prostate Cancer II

| PRJNA870438 | ENA

Landscape of Prostate-Specific Membrane Antigen Heterogeneity in Metastatic Prostate Cancer I

Project description:Landscape of Prostate-Specific Membrane Antigen Heterogeneity in Metastatic Prostate Cancer I

| PRJNA870437 | ENA

Mitochondrial Membrane Potential Identifies Cells with Enhanced Stemness for Cellular Therapy

Project description:Long-term survival and antitumor immunity of adoptively transferred CD8+ T cells is dependent on their metabolic fitness, but approaches to isolate therapeutic T cells based on metabolic features are not well established. Here we utilized a lipophilic cationic dye tetramethylrhodamine methyl ester (TMRM) to identify and isolate metabolically robust T cells based on their mitochondrial membrane potential (ΔΨm). Comprehensive metabolomic and gene expression profiling demonstrated global features of improved metabolic fitness in low-ΔΨm-sorted CD8+ T cells. Transfer of these low-ΔΨm T cells was associated with superior long-term in vivo persistence and an enhanced capacity to eradicate established tumors compared with high-ΔΨm cells. Use of ΔΨm-based sorting to enrich for cells with superior metabolic features was observed in CD8+, CD4+ T cell subsets, and long-term hematopoietic stem cells. This metabolism-based approach to cell selection may be broadly applicable to therapies involving the transfer of HSC or lymphocytes for the treatment of viral-associated illnesses and cancer.

2015-12-23 | GSE74001 | GEO

Pluripotent stem cell derived models of neurological diseases reveal early transcriptional heterogeneity

Project description:Identification of transcriptional heterogeneity changes in Huntington's disease (HD) and Autism Spectrum Disorder (ASD) human embryonic stem cells(hESC)- and induced pluripotent stem cells(iPSC)-derived neural progenitor cells

2021-02-14 | GSE138525 | GEO

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