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Lineage Tracing in Humans Enabled by Mitochondrial Mutations and Single-Cell Genomics.
Ludwig, Leif S; Lareau, Caleb A; Ulirsch, Jacob C; Christian, Elena; Muus, Christoph; Li, Lauren H; Pelka, Karin; Ge, Will; Oren, Yaara; Brack, Alison; Law, Travis; Rodman, Christopher; Chen, Jonathan H; Boland, Genevieve M; Hacohen, Nir; Rozenblatt-Rosen, Orit; Aryee, Martin J; Buenrostro, Jason D; Regev, Aviv; Sankaran, Vijay G.
Afiliação
  • Ludwig LS; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Division of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA. Electronic address: ludwig@broadinstitute.org.
  • Lareau CA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Division of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA; Molecular Pathology Unit, Massachusetts General Hospital, Charl
  • Ulirsch JC; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Division of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA; Program in Biological and Biomedical Sciences, Harvard Medical
  • Christian E; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Muus C; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.
  • Li LH; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Division of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
  • Pelka K; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Center for Cancer Research, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
  • Ge W; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Oren Y; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
  • Brack A; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Law T; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Rodman C; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Chen JH; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Boland GM; Center for Cancer Research, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
  • Hacohen N; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Center for Cancer Research, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
  • Rozenblatt-Rosen O; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Aryee MJ; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Molecular Pathology Unit, Massachusetts General Hospital, Charlestown, MA 02129, USA; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
  • Buenrostro JD; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Society of Fellows, Harvard University, Cambridge, MA 02138, USA.
  • Regev A; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Department of Biology and Koch Institute of Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: aregev@broadinstitute.org.
  • Sankaran VG; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Division of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA. Electron
Cell ; 176(6): 1325-1339.e22, 2019 03 07.
Article em En | MEDLINE | ID: mdl-30827679
ABSTRACT
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: DNA Mitocondrial / Mitocôndrias Limite: Humans Idioma: En Revista: Cell Ano de publicação: 2019 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: DNA Mitocondrial / Mitocôndrias Limite: Humans Idioma: En Revista: Cell Ano de publicação: 2019 Tipo de documento: Article