Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Systematic investigation of mitochondrial transfer between cancer cells and T cells at single-cell resolution

ABSTRACT: Mitochondrion (MT) as the energy-producing organelle participates in most metabolic activities of mammalian cells. Unidirectional mitochondrial transfer from T cells to cancer cells was recently observed “metabolically empowering” cancer cells while “depleting immune cells”, providing new insights into Tumor-T cell interaction and immune evasion. Here, we leveraged the increasingly adopted single-cell RNA-seq technology and introduced MERCI, a statistical deconvolution method for tracing and quantifying the process of mitochondrial trafficking between cancer and T cells. MERCI was benchmarked using data generated from a coculture system of MT-labeled cancer and T cells to accurately predict the recipient cells and their mitochondrial compositions. We independently demonstrated the cellular MT transfer signals and validated the MERCI performance by additionally generating a gold-standard mtscATAC-seq dataset. Application of MERCI to single cell human cancer samples identified a novel MT transfer phenotype and its signature genes involved in cytoskeleton remodeling, energy production and TNFα signaling pathways. Application of MERCI to ovarian cancer spatial transcriptomes revealed the prevalence of MT transfer in the tumor tissue of high T cell infiltration, which is elevated in the endothelium-rich regions. Finally, MT transfer is associated with high cell cycle activity and poor clinical outcome in our pan-cancer analysis through MERCI. In summary, MERCI enabled systematic investigation of a novel aspect of Tumor-T cell interaction and revealed MT-transfer related genes and pathways that may lead to new therapeutic opportunities.

ORGANISM(S): Mus musculus

PROVIDER: GSE235675 | GEO | 2024/06/21

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Epigenetic inheritance of diet-induced and sperm-borne mitochondrial RNAs

Project description:Spermatozoa harbor a complex and environment sensitive pool of small non-coding RNAs (sncRNA)1, which influences offspring development and adult phenotypes1-7. Whether spermatozoa in the epididymis are directly susceptible to environmental cues is not fully understood8. We used two distinct paradigms of preconception acute high fat diet to dissect epididymal vs testicular contributions to the sperm sncRNA pool and offspring health. We show that epididymal spermatozoa, but not developing germ cells, are sensitive to the environment and identify mitochondrial tRNAs and their fragments (mt-tsRNA) as sperm-borne factors. In humans, mt-tsRNAs in spermatozoa correlate with BMI and paternal overweight at conception doubles offspring obesity risk and compromises metabolic health. Sperm sncRNA-seq of mice mutant for genes involved in mitochondrial function, and metabolic phenotyping of their wild-type offspring, suggest that alterations of mt-tsRNAs are downstream of mitochondrial dysfunction. Most importantly, single embryo transcriptomics of genetically hybrid two-cell embryos demonstrated sperm-to-oocyte transfer of mt-tRNAs at fertilisation and implied them in the control of early embryo transcription. Our study supports the importance of paternal health at conception for offspring metabolism, shows that mt-tRNAs are diet-induced and sperm-borne and demonstrates, for the first time in a physiological setting, father-to-offspring transfer of sperm mitochondrial RNAs at fertilization.

2024-04-03 | GSE239815 | GEO

Prospective Approach to Deciphering the Impact of Intercellular Mitochondrial Transfer from Human Neural Stem Cells and Brain Tumor-Initiating Cells to Neighboring Astrocytes

Project description:The communication between neural stem cells (NSCs) and surrounding astrocytes is essential for the homeostasis of the NSC niche. Intercellular mitochondrial transfer, a unique communication system that utilizes the formation of tunneling nanotubes for targeted mitochondrial transfer be-tween donor and recipient cells, has recently been identified in a wide range of cell types. Intercel-lular mitochondrial transfer has also been observed between different types of cancer stem cells (CSCs) and their neighboring cells, including brain CSCs and astrocytes. CSC mitochondrial transfer significantly enhances overall tumor progression by reprogramming neighboring cells. Despite the urgent need to investigate this newly identified phenomenon, mitochondrial transfer in the central nervous system remains largely uncharacterized. In this study, we found evidence of intercellular mitochondrial transfer from human NSCs and from brain CSCs, also known as brain tumor-initiating cells (BTICs), to astrocytes in co-culture experiments. Both NSC and BTIC mito-chondria triggered similar transcriptome changes upon transplantation into the recipient astro-cytes. In contrast to NSCs, the transplanted mitochondria from BTICs had a significant prolifera-tive effect on the recipient astrocytes. This study forms the basis for mechanistically deciphering the impact of intercellular mitochondrial transfer on recipient astrocytes, which will potentially provide us with new insights into the mechanisms of mitochondrial retrograde signaling.

2024-01-24 | GSE254113 | GEO

EGAS00001000902-sc-20150424 - samples

Project description:Frequent somatic transfer of mitochondrial DNA into the nuclear genome of human cancer cells

| EGAD00001001351 | EGA

EGAS00001000165-sc-20150427 - samples

Project description:Frequent somatic transfer of mitochondrial DNA into the nuclear genome of human cancer cells

| EGAD00001001353 | EGA

EGAS00001000195-sc-20150424 - samples

Project description:Frequent somatic transfer of mitochondrial DNA into the nuclear genome of human cancer cells

| EGAD00001001350 | EGA

EGAS00001000160-sc-20150424 - samples

Project description:Frequent somatic transfer of mitochondrial DNA into the nuclear genome of human cancer cells

| EGAD00001001349 | EGA

Rare intercellular material transfer as a confound to interpreting inner retinal neuronal transplantation

Project description:Intercellular cytoplasmic material transfer (MT) occurs between transplanted and developing photoreceptors and ambiguates cell origin identification in developmental, transdifferentiation, and transplantation experiments. Whether MT is a photoreceptor-specific phenomenon is unclear. Retinal ganglion cell (RGC) replacement, through transdifferentiation or transplantation, holds potential for restoring vision in optic neuropathies. During careful assessment for MT following human stem cell-derived RGC transplantation into mice, we identified RGC xenografts occasionally giving rise to labeling of donor-derived cytoplasmic, nuclear, and mitochondrial proteins within recipient Müller glia. Critically, nuclear organization is distinct between human and murine retinal neurons, which enables unequivocal discrimination of donor from host cells. MT was dependent on internal limiting membrane disruption, which is also required for retinal engraftment following transplantation. Our findings demonstrate that retinal MT is not unique to photoreceptors and challenge the isolated use of species-specific immunofluorescent markers for xenotransplant identification. Assessment for MT is critical when analyzing neuronal replacement interventions.

2023-12-01 | GSE242537 | GEO

Balancing of mitochondrial translation through METTL8-mediated m3C modification of mitochondrial tRNAs

Project description:Mitochondria contain a specific translation machinery for the synthesis of respiratory chain components encoded on the mitochondrial genome. Mitochondrial tRNAs (mt-tRNAs) are also generated from the mitochondrial genome and, similar to their cytoplasmic counterparts, are modified at various positions. Here, we find that the RNA methyltransferase METTL8, is a mitochondrial protein that facilitates m3C methylation at position C32 of mt-tRNASer(UCN) and mt-tRNAThr. METTL8 knock out cells show reduced and over expressing cells enhanced respiratory chain activity. In pancreatic cancer, METTL8 levels are high, which correlates with patient survival. Indeed, METTL8 up regulation stimulates respiratory chain activity in these cells. Ribosome occupancy analysis using ribosome profiling revealed ribosome stalling on mt-tRNASer(UCN) and mt-tRNAThr codons and mass spectrometry analysis of native ribosomal subcomplexes unraveled reduced respiratory chain incorporation of the mitochondria encoded proteins ND6 and ND1. A well-balanced translation of mt-tRNASer(UCN) and mt-tRNAThr codons through METTL8-mediated C32 methylation might therefore provide optimal respiratory chain compositions and function.

2023-01-02 | GSE180400 | GEO

The human mitochondrial mRNA structurome reveals mechanisms of gene expression

Project description:The mammalian mitochondrial genome encodes thirteen proteins of the oxidative phosphorylation system, crucial in aerobic energy transduction. These proteins are translated from 9 monocistronic and 2 bicistronic transcripts, whose native structures remain unexplored, leaving fundamental molecular determinants of mitochondrial gene expression unknown. To address this knowledge gap, we developed a mitoDMS-MaPseq approach and used DREEM clustering to resolve the native mt-mRNA structurome in human mitochondria. In this way, we gained insights into mt-mRNA biology and translation regulatory mechanisms, including a unique translational frameshifting for the ATP8/ATP6 transcript. Furthermore, absence of the mt-mRNA maintenance factor LRPPRC led to a mitochondrial transcriptome structured differently, with specific mRNA regions exhibiting increased or decreased structuredness. This highlights the role of LRPPRC in maintaining mRNA folding to promote mt-mRNA stabilization and efficient translation. In conclusion, our mt-mRNA folding maps reveal novel mitochondrial gene expression mechanisms, serving as a detailed reference and tool for studying them in different physiological and pathological contexts.

2024-07-19 | GSE246523 | GEO

Mitochondrial RelA empowers mtDNA G-quadruplex formation for hypoxia adaptation in cancer cells

Project description:Mitochondrial DNA (mtDNA) G-quadruplexes (G4s) have been proposed as potential regulators of energy metabolism. However, numerous aspects of this process remain elusive. In our quest, employing a chemical-genetic screening strategy, we successfully identified the JAK/STAT3 pathway as the primary regulatory mechanism controlling mtDNA G4 dynamics in hypoxic MCF-7 cells. Further proteomic analyses and associated investigations have shed light on the translocation of RelA, a member of the NF-κB family, to the mitochondria upon activation of the JAK/STAT3 pathway. Once localized, RelA directly binds to mtDNA G4s and facilitates their folding, consequently yielding escalated mtDNA instability, impaired mtDNA transcription, and ensuing mitochondrial dysfunction. Ultimately, this intricately orchestrated cascade disrupts the equilibrium of energy metabolism, favoring a more pronounced deviation towards glycolysis. This pioneering revelation introduces an unprecedented and pivotal component to the intricately interconnected framework harnessed by cancer cells, empowering them to undergo metabolic reprogramming and adapt to hypoxic environments.

2024-05-13 | PXD043639 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data