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LINE-1 retrotransposons mediate cis-acting transcriptional control in human pluripotent stem cells and regulate early brain development

Adami, Anita LU orcid ; Garza, Raquel LU orcid ; Gerdes, Patricia LU orcid ; Johansson, Pia A LU ; Dorazehi, Fereshteh LU orcid ; Koutounidou, Symela LU ; Castilla-Vallmanya, Laura LU ; Atacho, Diahann A M LU orcid ; Sharma, Yogita LU and Johansson, Jenny G LU , et al. (2025) In Cell Genomics
Abstract

Long interspersed nuclear element 1 (L1) retrotransposons represent a vast source of genetic variability. However, mechanistic analysis of whether and how L1s contribute to human developmental programs is lacking, in part due to the challenges associated with specific profiling and manipulation of human L1 expression. Here, we show that thousands of hominoid-specific L1 integrants are expressed in human induced pluripotent stem cells and cerebral organoids. The activity levels of individual L1 promoters vary widely and correlate with an active epigenetic state. Efficient on-target CRISPR interference (CRISPRi) silencing of L1s revealed nearly a hundred co-opted L1-derived chimeric transcripts, and L1 silencing resulted in changes in... (More)

Long interspersed nuclear element 1 (L1) retrotransposons represent a vast source of genetic variability. However, mechanistic analysis of whether and how L1s contribute to human developmental programs is lacking, in part due to the challenges associated with specific profiling and manipulation of human L1 expression. Here, we show that thousands of hominoid-specific L1 integrants are expressed in human induced pluripotent stem cells and cerebral organoids. The activity levels of individual L1 promoters vary widely and correlate with an active epigenetic state. Efficient on-target CRISPR interference (CRISPRi) silencing of L1s revealed nearly a hundred co-opted L1-derived chimeric transcripts, and L1 silencing resulted in changes in neural differentiation programs and reduced cerebral organoid size. Together, these data implicate L1s and L1-derived transcripts in hominoid-specific CNS developmental processes.

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organization
publishing date
type
Contribution to journal
publication status
epub
subject
in
Cell Genomics
article number
100979
publisher
Cell Press
external identifiers
  • scopus:105015173791
  • pmid:40848716
ISSN
2666-979X
DOI
10.1016/j.xgen.2025.100979
language
English
LU publication?
yes
additional info
Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.
id
e1fa86e4-ebe0-4706-8b34-9f3c800da4a8
date added to LUP
2025-08-28 13:57:16
date last changed
2025-10-14 10:12:18
@article{e1fa86e4-ebe0-4706-8b34-9f3c800da4a8,
  abstract     = {{<p>Long interspersed nuclear element 1 (L1) retrotransposons represent a vast source of genetic variability. However, mechanistic analysis of whether and how L1s contribute to human developmental programs is lacking, in part due to the challenges associated with specific profiling and manipulation of human L1 expression. Here, we show that thousands of hominoid-specific L1 integrants are expressed in human induced pluripotent stem cells and cerebral organoids. The activity levels of individual L1 promoters vary widely and correlate with an active epigenetic state. Efficient on-target CRISPR interference (CRISPRi) silencing of L1s revealed nearly a hundred co-opted L1-derived chimeric transcripts, and L1 silencing resulted in changes in neural differentiation programs and reduced cerebral organoid size. Together, these data implicate L1s and L1-derived transcripts in hominoid-specific CNS developmental processes.</p>}},
  author       = {{Adami, Anita and Garza, Raquel and Gerdes, Patricia and Johansson, Pia A and Dorazehi, Fereshteh and Koutounidou, Symela and Castilla-Vallmanya, Laura and Atacho, Diahann A M and Sharma, Yogita and Johansson, Jenny G and Tam, Oliver and Kirkeby, Agnete and Barker, Roger A and Hammell, Molly Gale and Douse, Christopher H and Jakobsson, Johan}},
  issn         = {{2666-979X}},
  language     = {{eng}},
  month        = {{08}},
  publisher    = {{Cell Press}},
  series       = {{Cell Genomics}},
  title        = {{LINE-1 retrotransposons mediate cis-acting transcriptional control in human pluripotent stem cells and regulate early brain development}},
  url          = {{http://dx.doi.org/10.1016/j.xgen.2025.100979}},
  doi          = {{10.1016/j.xgen.2025.100979}},
  year         = {{2025}},
}