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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

Study of the heterogeneity of mammalian pluripotent stem cell lines (monkey ESC nhsmv)

Project description:study of the heterogeneity of mammalian pluripotent stem cell lines

2025-01-30 | E-MTAB-11995 | biostudies-arrayexpress

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

Genome wide transcriptional change by oligomycin or manipulation of mitochondrial membrane potential

Project description:Oligomycin, an inhibitor of ATP synthase (Complex V), increases mitochondrial membrane potential (ΔΨm) and induces ISR. Since direct manipulation of mitochondrial membrane potential using the genetic reagent that we developed (UCP1) rescued the effect of oligomycin on ISR, we performed RNAseq to investigate the effect of direct manipulation of ΔΨm by UCP1 on transcription. RNAseq analysis showed that direct manipulation of ΔΨm does not induce a major transcriptional program. However, oligomycin treatment caused a significant change in the expression of many genes, and the activation of UCP1 under oligomycin treatment rescued most of the transcriptional changes.

2025-04-22 | GSE254816 | GEO

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 I

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

| PRJNA870437 | 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