Young transposable elements rewired gene regulatory networks in human and chimpanzee hippocampal intermediate progenitors
File(s)
Published version
Author(s)
Patoori, Sruti
Barnada, Samantha M
Large, Christopher
Murray, John I
Trizzino, Marco
Type
Journal Article
Abstract
The hippocampus is associated with essential brain functions, such as learning and memory. Human hippocampal volume is significantly greater than expected compared with that of non-human apes, suggesting a recent expansion. Intermediate progenitors, which are able to undergo multiple rounds of proliferative division before a final neurogenic division, may have played a role in evolutionary hippocampal expansion. To investigate the evolution of gene regulatory networks underpinning hippocampal neurogenesis in apes, we leveraged the differentiation of human and chimpanzee induced pluripotent stem cells into TBR2 (or EOMES)-positive hippocampal intermediate progenitor cells (hpIPCs). We found that the gene networks active in hpIPCs are significantly different between humans and chimpanzees, with ∼2500 genes being differentially expressed. We demonstrate that species-specific transposon-derived enhancers contribute to these transcriptomic differences. Young transposons, predominantly endogenous retroviruses and SINE-Vntr-Alus (SVAs), were co-opted as enhancers in a species-specific manner. Human-specific SVAs provided substrates for thousands of novel TBR2-binding sites, and CRISPR-mediated repression of these SVAs attenuated the expression of ∼25% of the genes that are upregulated in human intermediate progenitors relative to the same cell population in the chimpanzee.
Date Issued
2022-10-04
Date Acceptance
2022-08-21
Citation
Development, 2022, 149 (19)
ISSN
0950-1991
Publisher
The Company of Biologists
Journal / Book Title
Development
Volume
149
Issue
19
Copyright Statement
© 2022. Published by The Company of Biologists Ltd This is an Open Access article distributed under the terms of the Creative Commons Attribution
License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use,
distribution and reproduction in any medium provided that the original work is properly attributed.
License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use,
distribution and reproduction in any medium provided that the original work is properly attributed.
License URL
Identifier
http://dx.doi.org/10.1242/dev.200413
Publication Status
Published
Article Number
dev200413
Date Publish Online
2022-10-04