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Heritable L1 retrotransposition in the mouse primordial germline and early embryo

Richardson, Sandra R ; Gerdes, Patricia LU orcid ; Gerhardt, Daniel J ; Sanchez-Luque, Francisco J ; Bodea, Gabriela-Oana ; Muñoz-Lopez, Martin ; Jesuadian, J Samuel ; Kempen, Marie-Jeanne H C ; Carreira, Patricia E and Jeddeloh, Jeffrey A , et al. (2017) In Genome Research 27(8). p.1395-1405
Abstract

LINE-1 (L1) retrotransposons are a noted source of genetic diversity and disease in mammals. To expand its genomic footprint, L1 must mobilize in cells that will contribute their genetic material to subsequent generations. Heritable L1 insertions may therefore arise in germ cells and in pluripotent embryonic cells, prior to germline specification, yet the frequency and predominant developmental timing of such events remain unclear. Here, we applied mouse retrotransposon capture sequencing (mRC-seq) and whole-genome sequencing (WGS) to pedigrees of C57BL/6J animals, and uncovered an L1 insertion rate of ≥1 event per eight births. We traced heritable L1 insertions to pluripotent embryonic cells and, strikingly, to early primordial germ... (More)

LINE-1 (L1) retrotransposons are a noted source of genetic diversity and disease in mammals. To expand its genomic footprint, L1 must mobilize in cells that will contribute their genetic material to subsequent generations. Heritable L1 insertions may therefore arise in germ cells and in pluripotent embryonic cells, prior to germline specification, yet the frequency and predominant developmental timing of such events remain unclear. Here, we applied mouse retrotransposon capture sequencing (mRC-seq) and whole-genome sequencing (WGS) to pedigrees of C57BL/6J animals, and uncovered an L1 insertion rate of ≥1 event per eight births. We traced heritable L1 insertions to pluripotent embryonic cells and, strikingly, to early primordial germ cells (PGCs). New L1 insertions bore structural hallmarks of target-site primed reverse transcription (TPRT) and mobilized efficiently in a cultured cell retrotransposition assay. Together, our results highlight the rate and evolutionary impact of heritable L1 retrotransposition and reveal retrotransposition-mediated genomic diversification as a fundamental property of pluripotent embryonic cells in vivo.

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publishing date
type
Contribution to journal
publication status
published
subject
keywords
Animals, Embryo, Mammalian/cytology, Female, Genomics/methods, Germ Cells, HeLa Cells, Humans, Long Interspersed Nucleotide Elements, Male, Mice, Mice, Inbred C57BL, Mosaicism, Whole Genome Sequencing/methods
in
Genome Research
volume
27
issue
8
pages
1395 - 1405
publisher
Cold Spring Harbor Laboratory Press (CSHL)
external identifiers
  • pmid:28483779
  • scopus:85026639648
ISSN
1549-5469
DOI
10.1101/gr.219022.116
language
English
LU publication?
no
additional info
© 2017 Richardson et al.; Published by Cold Spring Harbor Laboratory Press.
id
2344c88f-7088-4c11-8928-cc0c6d324b68
date added to LUP
2024-06-10 16:13:14
date last changed
2024-06-12 03:06:28
@article{2344c88f-7088-4c11-8928-cc0c6d324b68,
  abstract     = {{<p>LINE-1 (L1) retrotransposons are a noted source of genetic diversity and disease in mammals. To expand its genomic footprint, L1 must mobilize in cells that will contribute their genetic material to subsequent generations. Heritable L1 insertions may therefore arise in germ cells and in pluripotent embryonic cells, prior to germline specification, yet the frequency and predominant developmental timing of such events remain unclear. Here, we applied mouse retrotransposon capture sequencing (mRC-seq) and whole-genome sequencing (WGS) to pedigrees of C57BL/6J animals, and uncovered an L1 insertion rate of ≥1 event per eight births. We traced heritable L1 insertions to pluripotent embryonic cells and, strikingly, to early primordial germ cells (PGCs). New L1 insertions bore structural hallmarks of target-site primed reverse transcription (TPRT) and mobilized efficiently in a cultured cell retrotransposition assay. Together, our results highlight the rate and evolutionary impact of heritable L1 retrotransposition and reveal retrotransposition-mediated genomic diversification as a fundamental property of pluripotent embryonic cells in vivo.</p>}},
  author       = {{Richardson, Sandra R and Gerdes, Patricia and Gerhardt, Daniel J and Sanchez-Luque, Francisco J and Bodea, Gabriela-Oana and Muñoz-Lopez, Martin and Jesuadian, J Samuel and Kempen, Marie-Jeanne H C and Carreira, Patricia E and Jeddeloh, Jeffrey A and Garcia-Perez, Jose L and Kazazian, Haig H and Ewing, Adam D and Faulkner, Geoffrey J}},
  issn         = {{1549-5469}},
  keywords     = {{Animals; Embryo, Mammalian/cytology; Female; Genomics/methods; Germ Cells; HeLa Cells; Humans; Long Interspersed Nucleotide Elements; Male; Mice; Mice, Inbred C57BL; Mosaicism; Whole Genome Sequencing/methods}},
  language     = {{eng}},
  number       = {{8}},
  pages        = {{1395--1405}},
  publisher    = {{Cold Spring Harbor Laboratory Press (CSHL)}},
  series       = {{Genome Research}},
  title        = {{Heritable L1 retrotransposition in the mouse primordial germline and early embryo}},
  url          = {{http://dx.doi.org/10.1101/gr.219022.116}},
  doi          = {{10.1101/gr.219022.116}},
  volume       = {{27}},
  year         = {{2017}},
}