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| Status |
Public on Feb 28, 2019 |
| Title |
Human lineage tracing enabled by mitochondrial mutations and single cell genomics [Colonies_ATAC] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Lineage tracing provides unprecedented insights into the fate of individual cells and their progeny in complex organisms. While effective genetic approaches have been developed in vitro and in animal models, these cannot be used to interrogate human physiology in vivo. Instead, naturally occurring somatic mutations have been utilized to infer clonality and lineal relationships between cells in human tissues, but current approaches are limited by high error rates and scale, and provide little information about the state or function of the cells. Here, we show how somatic mutations in mitochondrial DNA (mtDNA) can be tracked by current single cell RNA-Seq (scRNA-Seq) or single cell ATAC-Seq (scATAC-Seq) for simultaneous analysis of single cell lineage and state. We leverage somatic mtDNA mutations as natural genetic barcodes and demonstrate their use as clonal markers to infer lineal relationships. We trace the lineage of human cells by somatic mtDNA mutations in a native context both in vitro and in vivo, and relate it to expression profiles and chromatin accessibility. Our approach should allow lineage tracing at a 100- to 1,000-fold greater scale than with single cell whole genome sequencing, while providing information on cell state, opening the way to chart detailed cell lineage and fate maps in human health and disease.
A variety of experimental designs using cells derived from both in vitro and in vivo to determine the efficacy of using mtDNA mutations in human clonal tracing.
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| Overall design |
Primary hematopoietic colonies were processed with bulk ATAC-seq
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| |
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| Contributor(s) |
Ludwig L, Lareau C |
| Citation(s) |
30827679 |
| Submission date |
Jun 01, 2018 |
| Last update date |
May 30, 2019 |
| 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 |
| |
|
| Platforms (2) |
| GPL15520 |
Illumina MiSeq (Homo sapiens) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
|
| Samples (40)
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| This SubSeries is part of SuperSeries: |
| GSE115218 |
Human lineage tracing enabled by mitochondrial mutations and single cell genomics |
|
| Relations |
| BioProject |
PRJNA474189 |
| SRA |
SRP149539 |
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