Ubiquitous L1 mosaicism in hippocampal neurons

Upton, Kyle R., Gerhardt, Daniel J., Jesuadian, J. Samuel, Richardson, Sandra R., Sanchez-Luque, Francisco J., Bodea, Gabriela O., Ewing, Adam D., Salvador-Palomeque, Carmen, van der Knaap, Mario S., Brennan, Paul M., Vanderver, Adeline and Faulkner, Geoffrey J. (2015) Ubiquitous L1 mosaicism in hippocampal neurons. Cell, 161 2: 228-239. doi:10.1016/j.cell.2015.03.026


Author Upton, Kyle R.
Gerhardt, Daniel J.
Jesuadian, J. Samuel
Richardson, Sandra R.
Sanchez-Luque, Francisco J.
Bodea, Gabriela O.
Ewing, Adam D.
Salvador-Palomeque, Carmen
van der Knaap, Mario S.
Brennan, Paul M.
Vanderver, Adeline
Faulkner, Geoffrey J.
Title Ubiquitous L1 mosaicism in hippocampal neurons
Journal name Cell   Check publisher's open access policy
ISSN 1097-4172
0092-8674
Publication date 2015-04-09
Year available 2015
Sub-type Article (original research)
DOI 10.1016/j.cell.2015.03.026
Open Access Status DOI
Volume 161
Issue 2
Start page 228
End page 239
Total pages 12
Place of publication Cambridge, MA United States
Publisher Cell Press (Elsevier)
Collection year 2016
Language eng
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.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Mater Research Institute-UQ (MRI-UQ)
Queensland Brain Institute Publications
Official 2016 Collection
 
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