Projects per year
Abstract
Induced pluripotent stem cells (iPSCs) can in principle differentiate into any cell of the body, and have revolutionized biomedical research and regenerative medicine. Unlike their human counterparts, mouse iPSCs (miPSCs) are reported to silence transposable elements and prevent transposable element-mediated mutagenesis. Here we apply short-read or Oxford Nanopore Technologies long-read genome sequencing to 38 bulk miPSC lines reprogrammed from 10 parental cell types, and 18 single-cell miPSC clones. While single nucleotide variants and structural variants restricted to miPSCs are rare, we find 83 de novo transposable element insertions, including examples intronic to Brca1 and Dmd. LINE-1 retrotransposons are profoundly hypomethylated in miPSCs, beyond other transposable elements and the genome overall, and harbor alternative protein-coding gene promoters. We show that treatment with the LINE-1 inhibitor lamivudine does not hinder reprogramming and efficiently blocks endogenous retrotransposition, as detected by long-read genome sequencing. These experiments reveal the complete spectrum and potential significance of mutations acquired by miPSCs.
Original language | English |
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Article number | 7470 |
Number of pages | 18 |
Journal | Nature Communications |
Volume | 13 |
Issue number | 1 |
DOIs | |
Publication status | Published - Dec 2022 |
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Dive into the research topics of 'Retrotransposon instability dominates the acquired mutation landscape of mouse induced pluripotent stem cells'. Together they form a unique fingerprint.Projects
- 2 Finished
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Natural and artificial regulation of the epigenome in pluripotency, cell identity, and development
Lister, R. (Investigator 01)
NHMRC National Health and Medical Research Council
1/01/20 → 31/12/24
Project: Research
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Epigenetic signatures of abnormal adult neurogenesis in Rett syndrome
Lister, R. (Investigator 01)
NHMRC National Health and Medical Research Council
1/01/17 → 31/12/19
Project: Research