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


Journal

Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066

Informations de publication

Date de publication:
07 03 2019
Historique:
received: 07 08 2018
revised: 29 11 2018
accepted: 09 01 2019
pmc-release: 07 03 2020
pubmed: 5 3 2019
medline: 7 1 2020
entrez: 5 3 2019
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 30827679
pii: S0092-8674(19)30055-8
doi: 10.1016/j.cell.2019.01.022
pmc: PMC6408267
mid: NIHMS1518665
pii:
doi:

Substances chimiques

Chromatin 0
DNA, Mitochondrial 0
Transposases EC 2.7.7.-

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1325-1339.e22

Subventions

Organisme : NIGMS NIH HHS
ID : T32 GM007226
Pays : United States
Organisme : NCI NIH HHS
ID : F31 CA232670
Pays : United States
Organisme : NHLBI NIH HHS
ID : R33 HL120791
Pays : United States
Organisme : NCI NIH HHS
ID : R33 CA202820
Pays : United States
Organisme : NHGRI NIH HHS
ID : K99 HG012579
Pays : United States
Organisme : NIAID NIH HHS
ID : U24 AI118672
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA207021
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA208756
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK103794
Pays : United States
Organisme : NHGRI NIH HHS
ID : RM1 HG006193
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright © 2019 Elsevier Inc. All rights reserved.

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Auteurs

Leif S 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.

Caleb A 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, Charlestown, MA 02129, USA; Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, MA 02115, USA.

Jacob C 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 School, Boston, MA 02115, USA.

Elena Christian (E)

Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

Christoph 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.

Lauren H 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.

Karin 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.

Will Ge (W)

Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

Yaara Oren (Y)

Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.

Alison Brack (A)

Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

Travis Law (T)

Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

Christopher Rodman (C)

Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

Jonathan H 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.

Genevieve M 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.

Nir 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.

Orit Rozenblatt-Rosen (O)

Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

Martin J 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.

Jason D Buenrostro (JD)

Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Society of Fellows, Harvard University, Cambridge, MA 02138, USA.

Aviv 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.

Vijay G 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. Electronic address: sankaran@broadinstitute.org.

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