Mitochondrial transfer from cancer cells induces cancer-associated fibroblast differentiation
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1113323 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR29079090_1.fastq.gz | Fastqsanger.gz | |||
| SRR29079090_2.fastq.gz | Fastqsanger.gz | |||
| SRR29079091_1.fastq.gz | Fastqsanger.gz | |||
| SRR29079091_2.fastq.gz | Fastqsanger.gz | |||
| SRR29079092_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 18 |
Similar Datasets
Project description:Cancer-associated fibroblasts (CAFs) are key components of the tumor microenvironment that commonly support cancer development and progression. Here we show that different cancer cells transfer mitochondria to fibroblasts in co-cultures and xenograft tumors, thereby inducing pro-tumorigenic CAF features. Transplantation of functional mitochondria from cancer cells induces metabolic alterations in fibroblasts, expression of CAF markers, and release of a pro-tumorigenic secretome and matrisome. These features promote tumor formation in pre-clinical mouse models. Mechanistically, the mitochondrial transfer requires the mitochondrial trafficking protein MIRO2. Its depletion in cancer cells suppresses mitochondrial transfer and inhibits CAF differentiation and tumor growth. The clinical relevance of these findings is reflected by the overexpression of MIRO2 in tumor cells at the leading edge of epithelial skin cancers. These results identify mitochondrial transfer from cancer cells to fibroblasts as a driver of tumorigenesis and provide a rationale for targeting MIRO2 and mitochondrial transfer in different malignancies.
2025-05-19 | GSE267826 | GEO
Project description: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.
2024-06-21 | GSE235675 | GEO
Project description:It has been reported that human mesenchymal stem cells (MSCs) can transfer mitochondria to the cells with severely compromised mitochondrial function. We tested whether MSCs transfer mitochondria to the cells under several different conditions of mitochondrial dysfunction, including human pathogenic mitochondrial DNA (mtDNA) mutations. Using biochemical selection methods, we found that exponentially growing cells in restrictive media (uridine and bromodeoxyuridine [BrdU]+) after coculture of MSCs (uridine-independent and BrdU-sensitive) and 143B-derived cells with severe mitochondrial dysfunction induced by either long-term ethidium bromide treatment or short-term rhodamine 6G (R6G) treatment (uridine-dependent but BrdU-resistant). The exponentially growing cells had nuclear DNA fingerprint patterns identical to 143B, and a sequence of mtDNA identical to the MSCs. Since R6G causes rapid and irreversible damage to mitochondria without the removal of mtDNA, the mitochondrial function appears to be restored through a direct transfer of mitochondria rather than mtDNA alone. Conditioned media, which were prepared by treating mtDNA-less 143B 0 cells under uridine-free condition, induced increased chemotaxis in MSC, which was also supported by transcriptome analysis. A chemotaxis inhibitory agent blocked mitochondrial transfer phenomenon in the above condition. However, we could not find any evidence of mitochondrial transfer to the cells harboring human pathogenic mtDNA mutations (A3243G mutation or 4,977 bp deletion). Thus, the mitochondrial transfer is limited to the condition of a near total absence of mitochondrial function. Elucidation of the mechanism of mitochondrial transfer will help us create a potential “cell therapy-based mitochondrial restoration or mitochondrial gene therapy” for human diseases caused by mitochondrial dysfunction. time series
2011-11-22 | E-GEOD-33831 | biostudies-arrayexpress
Project description:Non-alcoholic fatty liver is the most common liver disease worldwide. Here, we show that the mitochondrial protein mitofusin 2 (Mfn2) protects against liver disease. Reduced Mfn2 expression was detected in liver biopsies from patients with non-alcoholic steatohepatitis (NASH). Moreover, reduced Mfn2 levels were detected in mouse models of steatosis or NASH, and its re-expression in a NASH mouse model ameliorated the disease. Liver-specific ablation of Mfn2 in mice provoked inflammation, triglyceride accumulation, fibrosis, and liver cancer. We demonstrate that Mfn2 binds phosphatidylserine (PS) and can specifically extract PS into membrane domains, favoring PS transfer to mitochondria and mitochondrial phosphatidylethanolamine (PE) synthesis. Consequently, hepatic Mfn2 deficiency reduces PS transfer and phospholipid synthesis, leading to endoplasmic reticulum (ER) stress and the development of a NASH-like phenotype and liver cancer. Ablation of Mfn2 in liver reveals that disruption of ER-mitochondrial PS transfer is a new mechanism involved in the development of liver disease.
2018-01-25 | MTBLS600 | MetaboLights
Project description:Previous data revealed the role of Mfn2 in mediating mitochondrial transfer from a subset of astrocytes that express Dmp1 to cerebrovascular endothelial cells. We used scRNA-seq to investigate the role of Mfn2-mediated mitochondrial transfer in endothelial cell functions.
2024-07-31 | GSE210187 | GEO
Project description:METTL5 deficiency induces lung cancer regression via mitochondrial translation reduction
| PRJNA1136550 | ENA
Project description:Mitochondrial DNA (mtDNA) mutations are a major cause of maternally-inherited disease and have no treatment. Prevention strategies are critically important, but current clinical approaches are far from satisfactory. Legislation has changed in the UK to permit the development of mitochondrial transfer in human embryos, but major concerns have been raised about the mis-match of nuclear and mtDNA from ‘three parents’, with late sequelae being passed through the germ-line to subsequent generations. Matching donor and recipient mtDNA haplogroups is the proposed solution, but the effects of ‘haplogroup matching’ have not been tested experimentally. Here we show major changes in the cellular transcriptome both between and within the major mtDNA haplogroups when mitochondria are transferred between cells on a fixed nuclear genetic background. Larger differences were seen between phylogenetically related sub-haplogroups J1 and J2 which differ by only six nucleotides, than between the major haplogroups and known pathogenic mtDNA mutations. mtDNA transfer altered key cell signaling pathways, most notably the mTOR/Akt and the inflammatory cascade. This affected mitochondrial biogenesis, oxygen consumption, and ATP synthesis, and was blocked by rapamycin. These findings identify a key mediator in retrograde nuclear-mitochondrial signaling which is sensitive to subtle changes in mtDNA sequence. Given the established role of mTOR in cancer, neurodegeneration, and metabolic disease, this provides a mechanism for the association between inherited mtDNA variants and common late onset diseases, and demonstrates unexpected and dramatic effects of mitochondrial transfer not corrected by close haplogroup matching.
2023-06-07 | GSE74009 | GEO
Project description:Mitochondrial genomes are separated from the nuclear genome for most of the cell cycle by the nuclear double membrane, intervening cytoplasm and the mitochondrial double membrane. Despite these physical barriers we show that somatically acquired mitochondrial-nuclear genome fusion sequences are present in cancer cells. Most occur in conjunction with intranuclear genomic rearrangements and the features of the fusion fragments indicate that non-homologous end joining and/or replication-dependent DNA double strand break repair are the dominant mechanism involved. This study includes 12 pairs of whole-genome sequences (tumour and paired-normal), which present somatic mitochondrial DNA integrations in tumour genomes. Reference: Young Seok Ju et al., Frequent somatic transfer of mitochondrial DNA into the nuclear genome of human cancer cells, Genome Research (2015).
| EGAS00001001234 | EGA
Project description:To reveal an unappreciated mechanism of mitochondrial regulation of skeletal metabolic homeostasis via mitochondria transfer and provide new insights of the mechanism of glucocorticoid-induced osteoporosis progression.
2024-04-08 | GSE222961 | GEO
Project description:It has been reported that human mesenchymal stem cells (MSCs) can transfer mitochondria to the cells with severely compromised mitochondrial function. We tested whether MSCs transfer mitochondria to the cells under several different conditions of mitochondrial dysfunction, including human pathogenic mitochondrial DNA (mtDNA) mutations. Using biochemical selection methods, we found that exponentially growing cells in restrictive media (uridine- and bromodeoxyuridine [BrdU]+) after coculture of MSCs (uridine-independent and BrdU-sensitive) and 143B-derived cells with severe mitochondrial dysfunction induced by either long-term ethidium bromide treatment or short-term rhodamine 6G (R6G) treatment (uridine-dependent but BrdU-resistant). The exponentially growing cells had nuclear DNA fingerprint patterns identical to 143B, and a sequence of mtDNA identical to the MSCs. Since R6G causes rapid and irreversible damage to mitochondria without the removal of mtDNA, the mitochondrial function appears to be restored through a direct transfer of mitochondria rather than mtDNA alone. Conditioned media, which were prepared by treating mtDNA-less 143B rho0 cells under uridine-free condition, induced increased chemotaxis in MSC, which was also supported by transcriptome analysis. A chemotaxis inhibitory agent blocked mitochondrial transfer phenomenon in the above condition. However, we could not find any evidence of mitochondrial transfer to the cells harboring human pathogenic mtDNA mutations (A3243G mutation or 4,977 bp deletion). Thus, the mitochondrial transfer is limited to the condition of a near total absence of mitochondrial function. Elucidation of the mechanism of mitochondrial transfer will help us create a potential “cell therapy-based mitochondrial restoration or mitochondrial gene therapy” for human diseases caused by mitochondrial dysfunction.
2011-11-22 | GSE33831 | GEO