Kyle R Upton, Daniel J Gerhardt, Samuel J 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: Ubiquitous L1 mosaicism in hippocampal neurons. In: Cell, 161 (2), pp. 228–239, 2015.

Abstract

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.

BibTeX (Download)

@article{Upton2015-qu,
title = {Ubiquitous L1 mosaicism in hippocampal neurons},
author = {Kyle R Upton and Daniel J Gerhardt and Samuel J Jesuadian and Sandra R Richardson and Francisco J S\'{a}nchez-Luque and Gabriela O Bodea and Adam D Ewing and Carmen Salvador-Palomeque and Marjo S van der Knaap and Paul M Brennan and Adeline Vanderver and Geoffrey J Faulkner},
url = {http://dx.doi.org/10.1016/j.cell.2015.03.026},
year  = {2015},
date = {2015-04-01},
journal = {Cell},
volume = {161},
number = {2},
pages = {228--239},
abstract = {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.},
keywords = {Faulknerlab, Major_Publication},
pubstate = {published},
tppubtype = {article}
}