Transposable Element Activity Captures Human Pluripotent Cell States

Authors

Florencia Levin-Ferreyra
Srikanth Kodali
Yingzhi Cui
Alison R S Pashos
Patrizia Pessina
Justin Brumbaugh
Bruno Di Stefano

Language

English

Publication Date

1-1-2025

Journal

EMBO Reports

DOI

10.1038/s44319-024-00343-y

PMID

39668246

PMCID

PMC11772670

PubMedCentral® Posted Date

12-12-2024

PubMedCentral® Full Text Version

Post-print

Abstract

Human pluripotent stem cells (hPSCs) exist in multiple, transcriptionally distinct states and serve as powerful models for studying human development. Despite their significance, the molecular determinants and pathways governing these pluripotent states remain incompletely understood. Here, we demonstrate that transposable elements act as sensitive indicators of distinct pluripotent cell states. We engineered hPSCs with fluorescent reporters to capture the temporal expression dynamics of two state-specific transposable elements, LTR5_Hs, and MER51B. This dual reporter system enables real-time monitoring and isolation of stem cells transitioning from naïve to primed pluripotency and further towards differentiation, serving as a more accurate readout of pluripotency states compared to conventional systems. Unexpectedly, we identified a rare, metastable cell population within primed hPSCs, marked by transcripts related to preimplantation embryo development and which is associated with a DNA damage response. Moreover, our system establishes the chromatin factor NSD1 and the RNA-binding protein FUS as potent molecular safeguards of primed pluripotency. Our study introduces a novel system for investigating cellular potency and provides key insights into the regulation of embryonic development.

Keywords

Humans, Pluripotent Stem Cells, DNA Transposable Elements, Cell Differentiation, Genes, Reporter, Embryonic Development, Embryonic Stem Cells, Pluripotency, Totipotency, DNA Damage, Transposable Elements, DNA Replication, Recombination & Repair; Genetics, Gene Therapy & Genetic Disease; Stem Cells & Regenerative Medicine

Published Open-Access

yes

Recommended Citation

Levin-Ferreyra, Florencia; Kodali, Srikanth; Cui, Yingzhi; et al., "Transposable Element Activity Captures Human Pluripotent Cell States" (2025). Faculty and Staff Publications. 4854.
https://digitalcommons.library.tmc.edu/baylor_docs/4854