title: Ubiquitous L1 mosaicism in hippocampal neurons.
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.
authors: Mater Research Institute - University of Queensland, TRI Building, Woolloongabba QLD 4102, Australia.
authors: Kyle R
authors: KR
authors: Upton
authors: Mater Research Institute - University of Queensland, TRI Building, Woolloongabba QLD 4102, Australia.
authors: Daniel J
authors: DJ
authors: Gerhardt
authors: Mater Research Institute - University of Queensland, TRI Building, Woolloongabba QLD 4102, Australia.
authors: J Samuel
authors: JS
authors: Jesuadian
authors: Mater Research Institute - University of Queensland, TRI Building, Woolloongabba QLD 4102, Australia.
authors: Sandra R
authors: SR
authors: Richardson
authors: Mater Research Institute - University of Queensland, TRI Building, Woolloongabba QLD 4102, Australia.
authors: Francisco J
authors: FJ
authors: Sánchez-Luque
authors: Mater Research Institute - University of Queensland, TRI Building, Woolloongabba QLD 4102, Australia.
authors: Gabriela O
authors: GO
authors: Bodea
authors: Mater Research Institute - University of Queensland, TRI Building, Woolloongabba QLD 4102, Australia.
authors: Adam D
authors: AD
authors: Ewing
authors: Mater Research Institute - University of Queensland, TRI Building, Woolloongabba QLD 4102, Australia.
authors: Carmen
authors: C
authors: Salvador-Palomeque
authors: Department of Child Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, 1081 HV Amsterdam, The Netherlands.
authors: Marjo S
authors: MS
authors: van der Knaap
authors: Edinburgh Cancer Research Centre, Western General Hospital, Edinburgh, EH4 2XR, UK.
authors: Paul M
authors: PM
authors: Brennan
authors: Center for Genetic Medicine Research, Children's National Medical Center, Washington, DC 20010, USA.
authors: Adeline
authors: A
authors: Vanderver
authors: Mater Research Institute - University of Queensland, TRI Building, Woolloongabba QLD 4102, Australia; Queensland Brain Institute, University of Queensland, Brisbane QLD 4072, Australia. Electronic address: faulknergj@gmail.com.
authors: Geoffrey J
authors: GJ
authors: Faulkner
mesh_terms: D014644:Genetic Variation; D006624:Hippocampus / Q000166:cytology*; D006801:Humans; D020084:Long Interspersed Nucleotide Elements; D009030:Mosaicism; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology*; D016133:Polymerase Chain Reaction; D014015:Tissue Banks