Similar Datasets
Project description:Mitochondrial haplotype dependant T cell activity
| PRJNA1158737 | ENA
Project description:Ovarian aging leads to permanent reproductive senescence and systemic hormonal changes that predispose to age-associated comorbidities. Despite these clinical implications, the intrinsic mechanisms driving age-related ovarian decline are poorly defined. Mitochondrial DNA (mtDNA) mutations and instability are strongly associated with aging; however, it has not been established experimentally whether mitochondrial genetic diversity itself is a determinant of ovarian aging trajectories. To address this, we developed two genetically heterogeneous rat cohorts (OKC-HETB and OKC-HETW) that differ in mitochondrial haplotype while maintaining nuclear genome diversity. Our findings reveal that the OKC-HETW haplotype results in an accelerated loss of primordial follicle reserve and pathological stroma remodeling marked by fibrosis, macrophage infiltration, and the accumulation of multinucleated giant cells (MNGCs). These tissue-level pathologies were preceded by mitochondrial dysfunction, characterized by decreased respiratory complex activity, ATP production, and mtDNA copy number. Mechanistically, we identified a haplotype-specific defect in mitochondrial genome maintenance. Although TFAM protein levels were elevated, OKC-HETW ovaries showed reduced TFAM-mtDNA binding and suppressed TOMM20 abundance, implying that impaired TOMM20-mediated import leads to compromised mitochondrial genomic stability. Longitudinal transcriptomic and proteomic analyses further indicate that mitochondrial haplotype determines the rate of molecular aging, as OKC-HETW ovaries experience accelerated age-dependent activation of inflammatory and fibrotic pathways alongside suppression of proteostasis and mitochondrial function. These mitochondrial and molecular defects translated to reduced ovulation rates and impaired oocyte quality. Taken together, our findings pinpoint mitochondrial genetics as a key regulator of ovarian aging and putative target to preserve ovarian function and female healthspan.
2026-09-17 | GSE328056 | GEO
Project description:Comparison of gene expression for individuals affected with FCHL exhibiting the USF1 susceptibility haplotype and FCHL affected indiviuals carrying the protective haplotype Keywords: ordered
2004-02-29 | GSE590 | GEO
Project description:The 17q21.31 inversion locus is among the strongest genetic modifiers of tau-related neurodegenerative disease, yet its structure and function across ancestries remain incompletely understood. By integrating long-read sequencing, transcriptomics from postmortem human brain tissue, and iPSC-derived neurons and astrocytes, we identified H1_A, a previously unrecognized non-inverted H1 sub-haplotype enriched in individuals of African ancestry. H1_A carries rs8070723, a variant widely used to define the protective H2 haplotype, revealing limitations of current MAPT haplotype assignment in non-European populations. Across brain tissue and neural cell types, ancestry and haplotype influenced MAPT expression, tau isoform composition, extracellular matrix pathways, immune signaling, and oxidative stress responses. Functional studies further demonstrated effects on astrocyte migration and glutathione regulation. These findings uncover ancestry-dependent regulatory programs at 17q21.31 and provide a framework for more accurate interpretation of MAPT-associated risk in neurodegenerative disease.
2026-09-18 | GSE335405 | GEO
Project description:The 17q21.31 inversion locus is among the strongest genetic modifiers of tau-related neurodegenerative disease, yet its structure and function across ancestries remain incompletely understood. By integrating long-read sequencing, transcriptomics from postmortem human brain tissue, and iPSC-derived neurons and astrocytes, we identified H1_A, a previously unrecognized non-inverted H1 sub-haplotype enriched in individuals of African ancestry. H1_A carries rs8070723, a variant widely used to define the protective H2 haplotype, revealing limitations of current MAPT haplotype assignment in non-European populations. Across brain tissue and neural cell types, ancestry and haplotype influenced MAPT expression, tau isoform composition, extracellular matrix pathways, immune signaling, and oxidative stress responses. Functional studies further demonstrated effects on astrocyte migration and glutathione regulation. These findings uncover ancestry-dependent regulatory programs at 17q21.31 and provide a framework for more accurate interpretation of MAPT-associated risk in neurodegenerative disease.
2026-09-18 | GSE335293 | GEO
Project description:The 17q21.31 inversion locus is among the strongest genetic modifiers of tau-related neurodegenerative disease, yet its structure and function across ancestries remain incompletely understood. By integrating long-read sequencing, transcriptomics from postmortem human brain tissue, and iPSC-derived neurons and astrocytes, we identified H1_A, a previously unrecognized non-inverted H1 sub-haplotype enriched in individuals of African ancestry. H1_A carries rs8070723, a variant widely used to define the protective H2 haplotype, revealing limitations of current MAPT haplotype assignment in non-European populations. Across brain tissue and neural cell types, ancestry and haplotype influenced MAPT expression, tau isoform composition, extracellular matrix pathways, immune signaling, and oxidative stress responses. Functional studies further demonstrated effects on astrocyte migration and glutathione regulation. These findings uncover ancestry-dependent regulatory programs at 17q21.31 and provide a framework for more accurate interpretation of MAPT-associated risk in neurodegenerative disease.
2026-09-18 | GSE335291 | GEO
Project description:The 9p21.3 cardiovascular disease locus is the most influential common genetic risk factor for coronary artery disease, accounting for ~10-15% of disease among non-African populations. The ~60kb risk haplotype is human-specific and lacks coding genes, hindering efforts to decipher its function. Genetic studies implicate the 9p21.3 locus and other risk genes to effects in the vascular wall. Here, we use genome editing to delete the entire risk on non-risk haplotype from the genomes of human iPSCs and perform genomewide transcriptional profiling along the timecourse of their differentiation into vascular smooth muscle cells (VSMCs). These studies identify a network of ~3000 genes governed by the risk haplotype in VSMCs that predict deficits in cell division, adhesion and contraction, which we confirmufunctionally. Remarkably, deleting the risk haplotype reverts VSMCs to resemble the non-risk VSMCs, suggesting that the risk region drives a cell state transition. transcriptionally and functionally. . Deleting the risk haplotype reverts these cells to reverted to the non-risk of iPSCs we show that the non-risk haplotype has little effect on locus we produce iPSCs from risk and non-risk individuals, delete each haplotype using genome editing and generate vascular smooth muscle cells (VSMCs). We show that risk VSMCs exhibit aberrant adhesion and contraction, concomitant with dramatically altered global transcriptional changes that are enriched in previously identified cardiovascular disease genes and pathways. Unexpectedly, deleting the risk haplotype rescues VSMC transcriptional identity and function, while expressing the 9p21.3-associated long non-coding RNA ANRIL induces risk phenotypes in non-risk VSMCs. This studies shows that the risk haplotype dominantly predisposes VSMCs to adopt perturbed phenotypes associated with cardiovascular disease and establishes haplotype-edited iPSCs as powerful tools for functionally annotating human-specific variation in non-coding genomic regions.
2018-12-05 | GSE120099 | GEO
Project description:Developmental mitochondrial complex I activity determines lifespan
| PRJNA993400 | ENA
Project description:Mitochondrial activity tunes cellular resilience to excitotoxicity
| PRJNA1292848 | ENA
Project description:Comparison of gene expression for individuals affected with FCHL exhibiting the USF1 susceptibility haplotype and FCHL affected indiviuals carrying the protective haplotype
2007-09-28 | E-GEOD-590 | biostudies-arrayexpress