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| Status |
Public on May 04, 2023 |
| Title |
GTAC enables parallel genotyping of multiple genomic loci with chromatin accessibility profiling in single cells |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Understanding clonal evolution and cancer development requires experimental approaches for characterizing the consequences of somatic mutations on gene regulation. However, no methods currently exist that efficiently link chromatin accessibility with genotype in single cells. To address this, we developed Genotyping with the Assay for Transposase-Accessible Chromatin (GTAC), enabling accurate mutation detection at multiple amplified loci, coupled with robust chromatin accessibility readout. We applied GTAC to primary acute myeloid leukemia, obtaining high-quality chromatin accessibility profiles and clonal identities for multiple mutations in 88% of cells. We traced chromatin variation throughout clonal evolution, showing the restriction of different clones to distinct differentiation stages. Furthermore, we identified switches in transcription factors motif accessibility associated with a specific combination of driver mutations, which biased transformed progenitors towards a leukemia stem cell-like chromatin state. GTAC is a powerful tool to study clonal heterogeneity across a wide spectrum of pre-malignant and neoplastic conditions.
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| Overall design |
Plate-based single-cell ATAC-seq coupled with single-cell targeted genotyping of genomic loci. Results are from cell lines and primary human samples
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| Web link |
https://www.sciencedirect.com/science/article/pii/S1934590923001303?via%3Dihub
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| Contributor(s) |
Turkalj S, Jakobsen NA, Groom A, Metzner M, Usukhbayar B, Salazar MA, Clark K, Gur E, Hentges LD, Sopp P, Davies JJ, Hughes JR, Vyas P, Riva SG, Mickute G |
| Citation(s) |
37146586 |
| |
| Submission date |
Oct 04, 2022 |
| Last update date |
Aug 04, 2023 |
| Contact name |
Sven Turkalj |
| E-mail(s) |
sven.turkalj@kellogg.ox.ac.uk
|
| Phone |
07307186118
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| Organization name |
WIMM
|
| Department |
Radcliffe Department of Medicine
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| Lab |
Vyas Lab
|
| Street address |
John Radcliffe Hospital/Headley Way, Oxford OX3 9DS
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| City |
Oxford |
| ZIP/Postal code |
OX3 9DS |
| Country |
United Kingdom |
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| Platforms (2) |
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| Samples (5)
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| Relations |
| BioProject |
PRJNA887101 |
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