Mitochondrial variant enrichment from high-throughput single-cell RNA sequencing resolves clonal populations.

Autor: Miller TE; Department of Pathology, Massachusetts General Hospital, Boston, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA., Lareau CA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Department of Pathology, Stanford University, Stanford, CA, USA.; Department of Genetics, Stanford University, Stanford, CA, USA.; Division of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA., Verga JA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA., DePasquale EAK; Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Division of Hematology, Brigham and Women's Hospital, Department of Medicine, Harvard Medical School, Boston, MA, USA., Liu V; Department of Pathology, Stanford University, Stanford, CA, USA.; Department of Genetics, Stanford University, Stanford, CA, USA., Ssozi D; Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Division of Hematology, Brigham and Women's Hospital, Department of Medicine, Harvard Medical School, Boston, MA, USA., Sandor K; Department of Pathology, Stanford University, Stanford, CA, USA., Yin Y; Department of Pathology, Stanford University, Stanford, CA, USA., Ludwig LS; Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Division of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.; Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany., El Farran CA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA., Morgan DM; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA., Satpathy AT; Department of Pathology, Stanford University, Stanford, CA, USA., Griffin GK; Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA., Lane AA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.; Ludwig Center at Harvard, Harvard Medical School, Boston, MA, USA., Love JC; Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA., Bernstein BE; Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.; Ludwig Center at Harvard, Harvard Medical School, Boston, MA, USA.; Departments of Cell Biology and Pathology, Harvard Medical School, Boston, MA, USA., Sankaran VG; Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Division of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA., van Galen P; Broad Institute of MIT and Harvard, Cambridge, MA, USA. pvangalen@bwh.harvard.edu.; Division of Hematology, Brigham and Women's Hospital, Department of Medicine, Harvard Medical School, Boston, MA, USA. pvangalen@bwh.harvard.edu.; Ludwig Center at Harvard, Harvard Medical School, Boston, MA, USA. pvangalen@bwh.harvard.edu.
Jazyk: angličtina
Zdroj: Nature biotechnology [Nat Biotechnol] 2022 Jul; Vol. 40 (7), pp. 1030-1034. Date of Electronic Publication: 2022 Feb 24.
DOI: 10.1038/s41587-022-01210-8
Abstrakt: The combination of single-cell transcriptomics with mitochondrial DNA variant detection can be used to establish lineage relationships in primary human cells, but current methods are not scalable to interrogate complex tissues. Here, we combine common 3' single-cell RNA-sequencing protocols with mitochondrial transcriptome enrichment to increase coverage by more than 50-fold, enabling high-confidence mutation detection. The method successfully identifies skewed immune-cell expansions in primary human clonal hematopoiesis.
(© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Databáze: MEDLINE
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