Single-cell multi-omics of mitochondrial DNA disorders reveals dynamics of purifying selection across human immune cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA727567 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Other | ||||
| SRR14433330_1.fastq.gz | Fastqsanger.gz | |||
| SRR14433330_2.fastq.gz | Fastqsanger.gz | |||
| SRR14433331_1.fastq.gz | Fastqsanger.gz | |||
| SRR14433331_2.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 125 |
Similar Datasets
Project description:This SuperSeries is composed of the SubSeries listed below to reproduce the data and analyses from Lareau et al. 2023 Nature Genetics
2023-04-13 | GSE173936 | GEO
Project description:Pathogenic mutations in mitochondrial DNA (mtDNA) compromise cellular metabolism, contributing to cellular heterogeneity and disease. Diverse mutations are associated with diverse clinical phenotypes, suggesting distinct organ- and cell-type-specific metabolic vulnerabilities. Here we establish a multi-omics approach to quantify deletions in mtDNA alongside cell state features in single cells derived from six patients across the phenotypic spectrum of single large-scale mtDNA deletions (SLSMDs). By profiling 206,663 cells, we reveal the dynamics of pathogenic mtDNA deletion heteroplasmy consistent with purifying selection and distinct metabolic vulnerabilities across T-cell states in vivo and validate these observations in vitro. By extending analyses to hematopoietic and erythroid progenitors, we reveal mtDNA dynamics and cell-type-specific gene regulatory adaptations, demonstrating the context-dependence of perturbing mitochondrial genomic integrity. Collectively, we report pathogenic mtDNA heteroplasmy dynamics of individual blood and immune cells across lineages, demonstrating the power of single-cell multi-omics for revealing fundamental properties of mitochondrial genetics.
| S-EPMC10548551 | biostudies-literature
Project description:Large deletions in mitochondrial DNA (mtDNA) have been linked to a variety of clinical pathologies, including somatic emergence in congenital disorders such as Pearson Syndrome (MIM:557000), a mitochondrial disease characterized by sideroblastic anemia and exocrine pancreas dysfunction. Here, we develop a multi-omics approach to quantify mtDNA deletion heteroplasmy and cell state features in thousands of single cells. By profiling primary hematopoietic cells from three patients with Pearson Syndrome, we resolve the interdependence between pathogenic mtDNA heteroplasmy and cell lineage, including purifying selection against mtDNA deletions in effector-memory CD8 T-cell populations. We further observe widespread Pearson-specific transcriptomic changes in peripheral blood mononuclear cells. Additionally, single-cell analyses of in vivo and in vitro cultured bone marrow mononuclear cells reveal multi-faceted clonal dynamics and purifying selection in a patient with both Pearson Syndrome and Myelodysplastic Syndrome (MDS). Our results identify specific molecular perturbations underlying Pearson Syndrome and more generally provide a powerful framework to utilize multi-omics in the study of evolution in disease within single cells.
2023-04-14 | GSE217450 | GEO
Project description:Large deletions in mitochondrial DNA (mtDNA) have been linked to a variety of clinical pathologies, including somatic emergence in congenital disorders such as Pearson Syndrome (MIM:557000), a mitochondrial disease characterized by sideroblastic anemia and exocrine pancreas dysfunction. Here, we develop a multi-omics approach to quantify mtDNA deletion heteroplasmy and cell state features in thousands of single cells. By profiling primary hematopoietic cells from three patients with Pearson Syndrome, we resolve the interdependence between pathogenic mtDNA heteroplasmy and cell lineage, including purifying selection against mtDNA deletions in effector-memory CD8 T-cell populations. We further observe widespread Pearson-specific transcriptomic changes in peripheral blood mononuclear cells. Additionally, single-cell analyses of in vivo and in vitro cultured bone marrow mononuclear cells reveal multi-faceted clonal dynamics and purifying selection in a patient with both Pearson Syndrome and Myelodysplastic Syndrome (MDS). Our results identify specific molecular perturbations underlying Pearson Syndrome and more generally provide a powerful framework to utilize multi-omics in the study of evolution in disease within single cells.
2023-04-14 | GSE217449 | GEO
Project description:Large deletions in mitochondrial DNA (mtDNA) have been linked to a variety of clinical pathologies, including somatic emergence in congenital disorders such as Pearson Syndrome (MIM:557000), a mitochondrial disease characterized by sideroblastic anemia and exocrine pancreas dysfunction. Here, we develop a multi-omics approach to quantify mtDNA deletion heteroplasmy and cell state features in thousands of single cells. By profiling primary hematopoietic cells from three patients with Pearson Syndrome, we resolve the interdependence between pathogenic mtDNA heteroplasmy and cell lineage, including purifying selection against mtDNA deletions in effector-memory CD8 T-cell populations. We further observe widespread Pearson-specific transcriptomic changes in peripheral blood mononuclear cells. Additionally, single-cell analyses of in vivo and in vitro cultured bone marrow mononuclear cells reveal multi-faceted clonal dynamics and purifying selection in a patient with both Pearson Syndrome and Myelodysplastic Syndrome (MDS). Our results identify specific molecular perturbations underlying Pearson Syndrome and more generally provide a powerful framework to utilize multi-omics in the study of evolution in disease within single cells.
2023-04-14 | GSE217448 | GEO
Project description:Large deletions in mitochondrial DNA (mtDNA) have been linked to a variety of clinical pathologies, including somatic emergence in congenital disorders such as Pearson Syndrome (MIM:557000), a mitochondrial disease characterized by sideroblastic anemia and exocrine pancreas dysfunction. Here, we develop a multi-omics approach to quantify mtDNA deletion heteroplasmy and cell state features in thousands of single cells. By profiling primary hematopoietic cells from three patients with Pearson Syndrome, we resolve the interdependence between pathogenic mtDNA heteroplasmy and cell lineage, including purifying selection against mtDNA deletions in effector-memory CD8 T-cell populations. We further observe widespread Pearson-specific transcriptomic changes in peripheral blood mononuclear cells. Additionally, single-cell analyses of in vivo and in vitro cultured bone marrow mononuclear cells reveal multi-faceted clonal dynamics and purifying selection in a patient with both Pearson Syndrome and Myelodysplastic Syndrome (MDS). Our results identify specific molecular perturbations underlying Pearson Syndrome and more generally provide a powerful framework to utilize multi-omics in the study of evolution in disease within single cells.
2023-04-14 | GSE173933 | GEO
Project description:Large deletions in mitochondrial DNA (mtDNA) have been linked to a variety of clinical pathologies, including somatic emergence in congenital disorders such as Pearson Syndrome (MIM:557000), a mitochondrial disease characterized by sideroblastic anemia and exocrine pancreas dysfunction. Here, we develop a multi-omics approach to quantify mtDNA deletion heteroplasmy and cell state features in thousands of single cells. By profiling primary hematopoietic cells from three patients with Pearson Syndrome, we resolve the interdependence between pathogenic mtDNA heteroplasmy and cell lineage, including purifying selection against mtDNA deletions in effector-memory CD8 T-cell populations. We further observe widespread Pearson-specific transcriptomic changes in peripheral blood mononuclear cells. Additionally, single-cell analyses of in vivo and in vitro cultured bone marrow mononuclear cells reveal multi-faceted clonal dynamics and purifying selection in a patient with both Pearson Syndrome and Myelodysplastic Syndrome (MDS). Our results identify specific molecular perturbations underlying Pearson Syndrome and more generally provide a powerful framework to utilize multi-omics in the study of evolution in disease within single cells.
2023-04-14 | GSE173932 | GEO
Project description:Large deletions in mitochondrial DNA (mtDNA) have been linked to a variety of clinical pathologies, including somatic emergence in congenital disorders such as Pearson Syndrome (MIM:557000), a mitochondrial disease characterized by sideroblastic anemia and exocrine pancreas dysfunction. Here, we develop a multi-omics approach to quantify mtDNA deletion heteroplasmy and cell state features in thousands of single cells. By profiling primary hematopoietic cells from three patients with Pearson Syndrome, we resolve the interdependence between pathogenic mtDNA heteroplasmy and cell lineage, including purifying selection against mtDNA deletions in effector-memory CD8 T-cell populations. We further observe widespread Pearson-specific transcriptomic changes in peripheral blood mononuclear cells. Additionally, single-cell analyses of in vivo and in vitro cultured bone marrow mononuclear cells reveal multi-faceted clonal dynamics and purifying selection in a patient with both Pearson Syndrome and Myelodysplastic Syndrome (MDS). Our results identify specific molecular perturbations underlying Pearson Syndrome and more generally provide a powerful framework to utilize multi-omics in the study of evolution in disease within single cells.
2023-04-14 | GSE173931 | GEO
Project description:Large deletions in mitochondrial DNA (mtDNA) have been linked to a variety of clinical pathologies, including somatic emergence in congenital disorders such as Pearson Syndrome (MIM:557000), a mitochondrial disease characterized by sideroblastic anemia and exocrine pancreas dysfunction. Here, we develop a multi-omics approach to quantify mtDNA deletion heteroplasmy and cell state features in thousands of single cells. By profiling primary hematopoietic cells from three patients with Pearson Syndrome, we resolve the interdependence between pathogenic mtDNA heteroplasmy and cell lineage, including purifying selection against mtDNA deletions in effector-memory CD8 T-cell populations. We further observe widespread Pearson-specific transcriptomic changes in peripheral blood mononuclear cells. Additionally, single-cell analyses of in vivo and in vitro cultured bone marrow mononuclear cells reveal multi-faceted clonal dynamics and purifying selection in a patient with both Pearson Syndrome and Myelodysplastic Syndrome (MDS). Our results identify specific molecular perturbations underlying Pearson Syndrome and more generally provide a powerful framework to utilize multi-omics in the study of evolution in disease within single cells.
2023-04-14 | GSE173930 | GEO
Project description:Large deletions in mitochondrial DNA (mtDNA) have been linked to a variety of clinical pathologies, including somatic emergence in congenital disorders such as Pearson Syndrome (MIM:557000), a mitochondrial disease characterized by sideroblastic anemia and exocrine pancreas dysfunction. Here, we develop a multi-omics approach to quantify mtDNA deletion heteroplasmy and cell state features in thousands of single cells. By profiling primary hematopoietic cells from three patients with Pearson Syndrome, we resolve the interdependence between pathogenic mtDNA heteroplasmy and cell lineage, including purifying selection against mtDNA deletions in effector-memory CD8 T-cell populations. We further observe widespread Pearson-specific transcriptomic changes in peripheral blood mononuclear cells. Additionally, single-cell analyses of in vivo and in vitro cultured bone marrow mononuclear cells reveal multi-faceted clonal dynamics and purifying selection in a patient with both Pearson Syndrome and Myelodysplastic Syndrome (MDS). Our results identify specific molecular perturbations underlying Pearson Syndrome and more generally provide a powerful framework to utilize multi-omics in the study of evolution in disease within single cells.
2023-04-14 | GSE173935 | GEO