Lineage Tracing in Humans Enabled by Mitochondrial Mutations and Single-Cell Genomics.
chronic myeloid leukemia
colon cancer
hematopoiesis
lineage tracing
mitochondrial DNA
mtDNA
sequencing
single cell genomics
somatic mutations
Journal
Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066
Informations de publication
Date de publication:
07 03 2019
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.e22Subventions
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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