Young Transposable Elements Rewired Gene Regulatory Networks in Human and Chimpanzee Hippocampal Intermediate Progenitors

Authors

Sruti Patoori, Thomas Jefferson UniversityFollow
Samantha M Barnada, Thomas Jefferson UniversityFollow
Christopher Large, University of Pennsylvania
John I Murray, University of Pennsylvania
Marco Trizzino, marco.trizzino@jefferson.edu

Document Type

Article

Publication Date

10-1-2022

Comments

This article is the author’s final published version in Development (Cambridge, England), Volume 149, Issue 19, October 2022, Pages 1-16.

The published version is available at https://doi.org/10.1242/dev.200413. Copyright © Published by The Company of Biologists Ltd.

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.

Recommended Citation

Patoori, Sruti; Barnada, Samantha M; Large, Christopher; Murray, John I; and Trizzino, Marco, "Young Transposable Elements Rewired Gene Regulatory Networks in Human and Chimpanzee Hippocampal Intermediate Progenitors" (2022). Department of Biochemistry and Molecular Biology Faculty Papers. Paper 225.
https://jdc.jefferson.edu/bmpfp/225

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 License.

PubMed ID

36052683

Language

English