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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.

Cell, 2019-03, Vol.176 (6), p.1325-1339.e22 [Periódico revisado por pares]

United States: Elsevier Inc

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Título:
Lineage Tracing in Humans Enabled by Mitochondrial Mutations and Single-Cell Genomics
Autor: 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.
Assuntos: Base Sequence ; Cell Lineage ; Chromatin ; chronic myeloid leukemia ; colon cancer ; Colorectal Neoplasms - genetics ; Colorectal Neoplasms - pathology ; DNA, Mitochondrial - genetics ; Genomics - methods ; HEK293 Cells ; hematopoiesis ; Hematopoietic Stem Cells - physiology ; High-Throughput Nucleotide Sequencing - methods ; Humans ; lineage tracing ; Mitochondria - genetics ; mitochondrial DNA ; mtDNA ; Mutation ; sequencing ; single cell genomics ; Single-Cell Analysis ; somatic mutations ; Transposases
É parte de: Cell, 2019-03, Vol.176 (6), p.1325-1339.e22
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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Author contributions
Conceptualization, LSL with input from CAL, JCU, AR, and VGS; Methodology, LSL, CAL, JCU, KP, AR, and VGS; Formal Analysis, CAL, JCU, and LHL with input from LSL, MJA, JDB, AR, and VGS; Investigation, LSL, EC, CM, KP, WG, AB, TL, and CR; Resources, AR, VGS, MA, JDB, JHC, GMB, NH, and OR; Writing – Original Draft, LSL, CAL, JCU, AR, and VGS with input from all authors; Writing – Review & Editing, LSL, CAL, JCU, AR, and VGS with input from all authors; Visualization, CAL, JCU, LSL, and LHL; Supervision, AR and VGS; Project Administration, OR, AR, and VGS; Funding Acquisition, AR and VGS.
Descrição: 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. [Display omitted] •Somatic mtDNA mutations can track cellular relationships and hierarchies in vitro•Single-cell genomic assays faithfully detect mtDNA mutations•Lineage inference can be combined with gene expression or chromatin state profiles•mtDNA mutations enable studies of clonal architecture 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.
Editor: United States: Elsevier Inc
Idioma: Inglês

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Lineage Tracing in Humans Enabled by Mitochondrial Mutations and Single-Cell Genomics

United States: Elsevier Inc

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