Lineage Tracing in Humans Enabled by Mitochondrial Mutations and Single-Cell Genomics
Lineage tracing provides key insights into the fate of individual cells in complex organisms. Although effective genetic labeling approaches are available in model systems, in humans, most approaches require detection of nuclear somatic mutations, which have high error rates, limited scale, and do n...
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| Інші автори: | |
| Формат: | Стаття |
| Мова: | English |
| Опубліковано: |
Elsevier BV
2020
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| Онлайн доступ: | https://hdl.handle.net/1721.1/125306 |
| _version_ | 1826216677944066048 |
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| author | Regev, Aviv |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Regev, Aviv |
| author_sort | Regev, Aviv |
| collection | MIT |
| description | Lineage tracing provides key insights into the fate of individual cells in complex organisms. Although effective genetic labeling approaches are available in model systems, in humans, most approaches require detection of nuclear somatic mutations, which have high error rates, limited scale, and do not capture cell state information. Here, we show that somatic mutations in mtDNA can be tracked by single-cell RNA or assay for transposase accessible chromatin (ATAC) sequencing. We leverage somatic mtDNA mutations as natural genetic barcodes and demonstrate their utility as highly accurate clonal markers to infer cellular relationships. We track native human cells both in vitro and in vivo and relate clonal dynamics to gene expression and chromatin accessibility. Our approach should allow clonal tracking at a 1,000-fold greater scale than with nuclear genome sequencing, with simultaneous information on cell state, opening the way to chart cellular dynamics in human health and disease. Using single-cell sequencing technologies, somatic mutations in mtDNA can be used as natural genetic barcodes to study cellular states and clonal dynamics. |
| first_indexed | 2024-09-23T16:51:20Z |
| format | Article |
| id | mit-1721.1/125306 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T16:51:20Z |
| publishDate | 2020 |
| publisher | Elsevier BV |
| record_format | dspace |
| spelling | mit-1721.1/1253062022-10-03T08:45:48Z Lineage Tracing in Humans Enabled by Mitochondrial Mutations and Single-Cell Genomics Regev, Aviv Massachusetts Institute of Technology. Department of Biology Koch Institute for Integrative Cancer Research at MIT Lineage tracing provides key insights into the fate of individual cells in complex organisms. Although effective genetic labeling approaches are available in model systems, in humans, most approaches require detection of nuclear somatic mutations, which have high error rates, limited scale, and do not capture cell state information. Here, we show that somatic mutations in mtDNA can be tracked by single-cell RNA or assay for transposase accessible chromatin (ATAC) sequencing. We leverage somatic mtDNA mutations as natural genetic barcodes and demonstrate their utility as highly accurate clonal markers to infer cellular relationships. We track native human cells both in vitro and in vivo and relate clonal dynamics to gene expression and chromatin accessibility. Our approach should allow clonal tracking at a 1,000-fold greater scale than with nuclear genome sequencing, with simultaneous information on cell state, opening the way to chart cellular dynamics in human health and disease. Using single-cell sequencing technologies, somatic mutations in mtDNA can be used as natural genetic barcodes to study cellular states and clonal dynamics. National Institutes of Health (U.S.) (Grant R33 CA202820) 2020-05-19T14:09:46Z 2020-05-19T14:09:46Z 2019-03 2020-03-17T17:22:00Z Article http://purl.org/eprint/type/JournalArticle 0092-8674 https://hdl.handle.net/1721.1/125306 Ludwig, Leif S. et al. “Lineage Tracing in Humans Enabled by Mitochondrial Mutations and Single-Cell Genomics.” Cell 176 (2019): 1325-1339.e22 © 2019 The Author(s) en 10.1016/J.CELL.2019.01.022 Cell Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier BV PMC |
| spellingShingle | Regev, Aviv Lineage Tracing in Humans Enabled by Mitochondrial Mutations and Single-Cell Genomics |
| title | Lineage Tracing in Humans Enabled by Mitochondrial Mutations and Single-Cell Genomics |
| title_full | Lineage Tracing in Humans Enabled by Mitochondrial Mutations and Single-Cell Genomics |
| title_fullStr | Lineage Tracing in Humans Enabled by Mitochondrial Mutations and Single-Cell Genomics |
| title_full_unstemmed | Lineage Tracing in Humans Enabled by Mitochondrial Mutations and Single-Cell Genomics |
| title_short | Lineage Tracing in Humans Enabled by Mitochondrial Mutations and Single-Cell Genomics |
| title_sort | lineage tracing in humans enabled by mitochondrial mutations and single cell genomics |
| url | https://hdl.handle.net/1721.1/125306 |
| work_keys_str_mv | AT regevaviv lineagetracinginhumansenabledbymitochondrialmutationsandsinglecellgenomics |