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| Status |
Public on Jul 13, 2020 |
| Title |
High-throughput single-cell mitochondrial DNA genotyping reveals properties of clonal variation in human contexts [CD34-invitro] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Natural mitochondrial DNA (mtDNA) sequence variation plays a fundamental role in human disease and enables the clonal tracing of native human cells. While various genotyping approaches revealed mutational heterogeneity in human tissues and single cells, current methodologies are limited by scale. Here, we introduce a high-throughput, droplet-based mitochondrial single-cell Assay for Transposase Accessible Chromatin with sequencing (mtscATAC-seq) protocol and computational framework that facilitate high-confidence mtDNA mutation calling in thousands of single cells. Further, the concomitant high-quality accessible chromatin readout enables the paired inference of individual cell mtDNA heteroplasmy, clonal lineage, cell state, and accessible chromatin regulatory features. Our multi-omic analyses reveals single-cell variation in heteroplasmy of a pathologic mtDNA variant (m.8344A>G), which we tie to intra-individual chromatin variability and clonal evolution. Further, using somatic mtDNA mutations, we clonally trace thousands of hematopoietic cells in vitro and in patients with chronic lymphocytic leukemia, linking epigenomic variability to subclonal evolution in vivo.
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| Overall design |
~500 or 800 CD34+ hematopoietic stem and progenitor cells were clonally expanded in two independent cultures before differentiating cells in the presence of erythropoietin, stem cell factor and interleukin-3.
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| Contributor(s) |
Lareau C, Ludwig L |
| Citation missing |
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| Submission date |
Dec 30, 2019 |
| Last update date |
Jul 13, 2020 |
| Contact name |
Caleb Lareau |
| E-mail(s) |
lareauc@mskcc.org
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| Organization name |
Memorial Sloan Kettering
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| Street address |
417 E 68th St, Zuckerman - ZRC 1132
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| City |
New York |
| State/province |
New York |
| ZIP/Postal code |
10065 |
| Country |
USA |
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| Platforms (1) |
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| Samples (5)
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| This SubSeries is part of SuperSeries: |
| GSE142745 |
High-throughput single-cell mitochondrial DNA genotyping reveals properties of clonal variation in human contexts |
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| Relations |
| BioProject |
PRJNA598174 |
| SRA |
SRP239087 |
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