L1 Retrotransposition in Human Neural Progenitor Cells

By Nicole G. Coufal, Jose Luis Garcia-Perez, Grace E. Peng, Gene W. Yeo, Yangling Mu, Michael T. Lovci, M. Morell, K. O'shea, J. V. Moran, Fred H. Gage. Nature, 2009

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Long interspersed element 1 (LINE-1 or L1) retrotransposons have markedly affected the human genome. L1s must retrotranspose in the germ line or during early development to ensure their evolutionary success, yet the extent to which this process affects somatic cells is poorly understood. We previously demonstrated that engineered human L1s can retrotranspose in adult rat hippocampus progenitor cells in vitro and in the mouse brain in vivo. Here we demonstrate that neural progenitor cells isolated from human fetal brain and derived from human embryonic stem cells support the retrotransposition of engineered human L1s in vitro. Furthermore, we developed a quantitative multiplex polymerase chain reaction that detected an increase in the copy number of endogenous L1s in the hippocampus, and in several regions of adult human brains, when compared to the copy number of endogenous L1s in heart or liver genomic DNAs from the same donor. These data suggest that de novo L1 retrotransposition events may occur in the human brain and, in principle, have the potential to contribute to individual somatic mosaicism.

Subfields: Molecular Biology, Plant Science

View Paper: https://www.semanticscholar.org/paper/b6f9f80984e9095ff0c9544b9d97f988494b8ec6

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Citations in the corpus

LINE-1 Elements in Structural Variation and Disease (2011, methodology): “ORF1p and/or L1 RNA also have been detected in human oocytes, in some human somatic cells, and at select times during human and mouse germ cell development (21, 29, 54, 85, 236).”
Cellular heterogeneity: when do differences make a difference? (2010, background): “…of a specific molecule from a large repertoire of possibilities generates enormous diversity by individual cell variation, such as seen for odorant, cell adhesion, or immune molecules (Coufal et al., 2009; Lomvardas et al., 2006; Morishita and Yagi, 2007; Muotri et al., 2005; Ribich et al., 2006).”
Transposition Driven Genomic Heterogeneity in the Drosophila Brain: A Dissertation (2012, neutral): “2 Several reports have indicated that specific regions of the mammalian brain, most evidently the hippocampus, might be particularly predisposed to LINE-1 (L1) element retrotransposition (Coufal et al., 2009; Baillie et al., 2011).”
LINE-1 derepression in senescent cells triggers interferon and inflammaging (2019, positive): “1b) were developed by Coufal et al. (2009) 16 to preferentially target L1HS.”
Candidate Genes and Political Behavior (2012, background): “…genes” comprise 45% of the human genome, move about the genome by a copy-and-paste mechanism changing DNA content and structure, are regulated by the epigenome (and hence are potentially environmentally responsive), and appear to be particularly prevalent in the human brain (Coufal et al. 2009).”
Somatic retrotransposition alters the genetic landscape of the human brain (2011, methodology): “Previous works have equated L1 CNV with somatic mobilization in vivo 10-11 .”
The Cellular and Molecular Landscapes of the Developing Human Central Nervous System (2016, neutral): “mobile DNA elements play a role in the generation of diversity and complexity in the developing human brain (Coufal et al., 2009).”