Ubiquitous L1 Mosaicism in Hippocampal Neurons

Kyle R. Upton, Daniel J. Gerhardt, J. Samuel Jesuadian, Sandra R. Richardson, Francisco J. Sánchez-Luque, Gabriela O. Bodea, Adam D. Ewing, Carmen Salvador-Palomeque, Marjo S. van der Knaap, Paul M. Brennan, Adeline Vanderver, Geoffrey J. Faulkner

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Somatic LINE-1 (L1) retrotransposition during neurogenesis is a potential source of genotypic variation among neurons. As a neurogenic niche, the hippocampus supports pronounced L1 activity. However, the basal parameters and biological impact of L1-driven mosaicism remain unclear. Here, we performed single-cell retrotransposon capture sequencing (RC-seq) on individual human hippocampal neurons and glia, as well as cortical neurons. An estimated 13.7 somatic L1 insertions occurred per hippocampal neuron and carried the sequence hallmarks of target-primed reverse transcription. Notably, hippocampal neuron L1 insertions were specifically enriched in transcribed neuronal stem cell enhancers and hippocampus genes, increasing their probability of functional relevance. In addition, bias against intronic L1 insertions sense oriented relative to their host gene was observed, perhaps indicating moderate selection against this configuration in vivo. These experiments demonstrate pervasive L1 mosaicism at genomic loci expressed in hippocampal neurons.

Original languageEnglish
Pages (from-to)228-239
Number of pages12
JournalCell
Volume161
Issue number2
DOIs
Publication statusPublished - 9 Apr 2015

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