Somatic mosaicism in neuronal precursor cells mediated by L1 retrotransposition.
Revealing the mechanisms for neuronal somatic diversification remains a central challenge for understanding individual differences in brain organization and function. Here we show that an engineered human LINE-1 (for long interspersed nuclear element-1; also known as L1) element can retrotranspose in neuronal precursors derived from rat hippocampus neural stem cells. The resulting retrotransposition events can alter the expression of neuronal genes, which, in turn, can influence neuronal cell fate in vitro. We further show that retrotransposition of a human L1 in transgenic mice results in neuronal somatic mosaicism. The molecular mechanism of action is probably mediated through Sox2, because a decrease in Sox2 expression during the early stages of neuronal differentiation is correlated with increases in both L1 transcription and retrotransposition. Our data therefore indicate that neuronal genomes might not be static, but some might be mosaic because of de novo L1 retrotransposition events.
Muotri
Alysson R
AR
Laboratory of Genetics, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.
Chu
Vi T
VT
Marchetto
Maria C N
MC
Deng
Wei
W
Moran
John V
JV
Gage
Fred H
FH
D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D024002:HMGB Proteins / Q000235:genetics; D006801:Humans; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009030:Mosaicism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011995:Recombination, Genetic / Q000235:genetics*; D018626:Retroelements / Q000235:genetics*; D055748:SOXB1 Transcription Factors; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics
D004268:DNA-Binding Proteins; D024002:HMGB Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D018626:Retroelements; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; C527784:Sox2 protein, rat; D014157:Transcription Factors; C485184:enhanced green fluorescent protein; C033652:postsynaptic density proteins; D049452:Green Fluorescent Proteins