Transposable element expression and sub-cellular dynamics during hPSC differentiation to endoderm, mesoderm, and ectoderm lineages

Isaac A. Babarinde, Xiuling Fu, Gang Ma, Yuhao Li, Zhangting Liang, Jianfei Xu, Zhen Xiao, Yu Qiao, Zheng Lin, Katerina Oleynikova, Mobolaji T. Akinwole, Xuemeng Zhou, Alexey Ruzov and Andrew P. Hutchins ()
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Isaac A. Babarinde: Southern University of Science and Technology
Xiuling Fu: Southern University of Science and Technology
Gang Ma: Southern University of Science and Technology
Yuhao Li: Southern University of Science and Technology
Zhangting Liang: Southern University of Science and Technology
Jianfei Xu: Southern University of Science and Technology
Zhen Xiao: Southern University of Science and Technology
Yu Qiao: Southern University of Science and Technology
Zheng Lin: Southern University of Science and Technology
Katerina Oleynikova: Russian Academy of Sciences
Mobolaji T. Akinwole: University of Ibadan
Xuemeng Zhou: Southern University of Science and Technology
Alexey Ruzov: Russian Academy of Sciences
Andrew P. Hutchins: Southern University of Science and Technology

Nature Communications, 2025, vol. 16, issue 1, 1-24

Abstract: Abstract Transposable elements (TEs) are genomic elements present in multiple copies in mammalian genomes. TEs were thought to have little functional relevance but recent studies report roles in biological processes, including embryonic development. To investigate the expression dynamics of TEs during human early development, we generated long-read sequence data from human pluripotent stem cells (hPSCs) in vitro differentiated to endoderm, mesoderm, and ectoderm lineages to construct lineage-specific transcriptome assemblies and accurately place TE sequences. Our analysis reveals that specific TE superfamilies exhibit distinct expression patterns. Notably, we observed TE switching, where the same family of TE is expressed in multiple cell types, but originates from different transcripts. Interestingly, TE-containing transcripts exhibit distinct levels of transcript stability and subcellular localization. Moreover, TE-containing transcripts increasingly associate with chromatin in germ layer cells compared to hPSCs. This study suggests that TEs contribute to human embryonic development through dynamic chromatin interactions.

Date: 2025
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DOI: 10.1038/s41467-025-63080-3

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