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| Status |
Public on Apr 14, 2023 |
| Title |
Cellular states, clonal dynamics, and evolution in Pearson syndrome revealed via single-cell multi-omics [Invitro_scRNA] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
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.
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| Overall design |
Bone marrow mononuclear cells were obtained from a human patient, in vitro differentiated and processed for single cell genomics
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| |
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| Contributor(s) |
Lareau C, Ludwig L |
| Citation(s) |
37386249 |
| |
| Submission date |
May 05, 2021 |
| Last update date |
Jul 14, 2023 |
| Contact name |
Caleb Lareau |
| E-mail(s) |
lareauc@mskcc.org
|
| Organization name |
Memorial Sloan Kettering
|
| Street address |
417 E 68th St, Zuckerman - ZRC 1132
|
| City |
New York |
| State/province |
New York |
| ZIP/Postal code |
10065 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (8)
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| This SubSeries is part of SuperSeries: |
| GSE173936 |
Single-cell multi-omics of mitochondrial DNA disorders reveals dynamics of purifying selection across human immune cells |
|
| Relations |
| BioProject |
PRJNA727573 |
| SRA |
SRP318594 |
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