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PreprintCC BYbioRxiv

Comparison of cell-cycle gene expression dynamics and mRNA kinetics across mouse and human pluripotent systems

  1. 1Institut de Genetique et de Biologie Moleculaire et Cellulaire

Abstract

Cell-cycle remodeling is fundamental to pluripotency and lineage commitment, yet whether its transcriptional and post-transcriptional architecture is conserved across species and developmental states has remained unresolved. Here we introduce Ciclopes, a biology-informed deep-learning framework that resolves continuous cell-cycle phase and phase-dependent mRNA transcription and degradation directly from single-cell RNA sequencing. Applying Ciclopes across six mouse and human pluripotent stem-cell systems spanning naive and primed states, we uncover striking divergence in transcriptional complexity and oscillatory control: mouse systems sustain elevated baseline expression of core cell-cycle regulators, while human systems trade higher baseline expression for larger oscillatory amplitude. Strikingly, mRNA degradation timing remain far more conserved across systems than transcription timing, exposing post-transcriptional regulation as a stable evolutionary backbone. As human iPSCs differentiate into definitive endoderm, cells progressively exit the cell cycle, cell-cycle-coupled gene networks contract, and surviving regulators oscillate with larger amplitude. Ciclopes establishes a general framework for dissecting how pluripotent cells tune proliferation across evolutionary and developmental transitions.

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BibTeX
@misc{nariya2026comparison,
  title = {{Comparison of cell-cycle gene expression dynamics and mRNA kinetics across mouse and human pluripotent systems}},
  author = {M. K. Nariya and D. Santiago-Algarra and G. Zanardelli and I. K. Boudjelthia and T. Ye and C. Thibault-Carpentier and S. Jarriault and N. Molina},
  howpublished = {bioRxiv},
  year = {2026},
  month = sep,
  doi = {10.64898/2026.09.14.751360},
  url = {https://www.biorxiv.org/content/10.64898/2026.09.14.751360v1},
  note = {CC BY},
}
RIS
TY  - UNPB
TI  - Comparison of cell-cycle gene expression dynamics and mRNA kinetics across mouse and human pluripotent systems
AU  - M. K. Nariya
AU  - D. Santiago-Algarra
AU  - G. Zanardelli
AU  - I. K. Boudjelthia
AU  - T. Ye
AU  - C. Thibault-Carpentier
AU  - S. Jarriault
AU  - N. Molina
PY  - 2026
DA  - 2026/09/14
PB  - bioRxiv
DO  - 10.64898/2026.09.14.751360
UR  - https://www.biorxiv.org/content/10.64898/2026.09.14.751360v1
AB  - Cell-cycle remodeling is fundamental to pluripotency and lineage commitment, yet whether its transcriptional and post-transcriptional architecture is conserved across species and developmental states has remained unresolved. Here we introduce Ciclopes, a biology-informed deep-learning framework that resolves continuous cell-cycle phase and phase-dependent mRNA transcription and degradation directly from single-cell RNA sequencing. Applying Ciclopes across six mouse and human pluripotent stem-cell systems spanning naive and primed states, we uncover striking divergence in transcriptional complexity and oscillatory control: mouse systems sustain elevated baseline expression of core cell-cycle regulators, while human systems trade higher baseline expression for larger oscillatory amplitude. Strikingly, mRNA degradation timing remain far more conserved across systems than transcription timing, exposing post-transcriptional regulation as a stable evolutionary backbone. As human iPSCs differentiate into definitive endoderm, cells progressively exit the cell cycle, cell-cycle-coupled gene networks contract, and surviving regulators oscillate with larger amplitude. Ciclopes establishes a general framework for dissecting how pluripotent cells tune proliferation across evolutionary and developmental transitions.
ER  -