Biology subjects

Jarriault, S.

Publications and source records attributed to Jarriault, S..

3 recordsLinked to original sources

bioRxiv2026

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

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.

systems biology↗

bioRxiv2024

Essential and dual effects of Notch activity on a natural transdifferentiation event

Cell identity can be reprogrammed, naturally or experimentally, albeit with low frequency. Why given cells, but not their neighbours, undergo a cell identity conversion remains unclear. We find that Notch signalling plays a key role to promote natural transdifferentiation in C. elegans. Endogenous Notch signal endows a cell with the competence to transdifferentiate by promoting plasticity factors expression (hlh-16/Olig and sem-4/Sall). Strikingly, exogenous Notch can trigger ectopic transdifferentiation in vivo. However, Notch signalling can both promote and block transdifferentiation depending on its activation timing. Notch only promotes transdifferentiation during an early precise window of opportunity and signal duration must be tightly controlled in time. Our findings emphasise the importance of temporality and dynamics of the underlying molecular events preceding the initiation of natural cell reprogramming. Finally, our results support a model where both an extrinsic signal and the intrinsic cellular context combine to empower a cell with the competence to transdifferentiate.

developmental biology↗

bioRxiv2020

Tissue-specific transcription footprinting using RNA PoI DamID (RAPID) in C. elegans

Differential gene expression across cell types underlies the development and cell physiology in multicellular organisms. C. elegans is a powerful, extensively used model to address these biological questions. A remaining bottleneck relates, however, to the difficulty to obtain comprehensive tissue-specific gene transcription data, since available methods are still challenging to execute and/or require large worm populations. Here, we introduce the RNA PoI DamID (RAPID) approach, in which the Dam methyltransferase is fused to a ubiquitous RNA polymerase subunit in order to create transcriptional footprints via methyl marks on the DNA of transcribed genes. To validate the method, we determined the polymerase footprints in whole animals, sorted embryonic blastomeres and in different tissues from intact young adults by driving Dam fusion expression tissue-specifically. We obtained meaningful transcriptional footprints in line with RNA-seq studies in whole animals or specific tissues. To challenge the sensitivity of RAPID and demonstrate its utility to determine novel tissue-specific transcriptional profiles, we determined the transcriptional footprints of the pair of XXX neuroendocrine cells, representing 0.2% of the somatic cell content of the animals. We identified 2362 candidate genes with putatively active transcription in XXX cells, among which the few known markers for these cells. Using transcriptional reporters for a subset of new hits, we confirmed that the majority of them were expressed in XXX and identified novel XXX-specific markers. Taken together, our work establishes RAPID as a valid method for the determination of polymerase footprints in specific tissues of C. elegans without the need for cell sorting or RNA tagging. Article summaryGene expression is a major determinant of cell fate and physiology, yet it is notoriously difficult to characterize in individual cell types for the widely used model system C. elegans. Here, we introduce a method based on the in vivo covalent modification of DNA by transcribing RNA polymerases to determine genome-wide transcription patterns in single tissues of embryos or young adult animals. We show that the method is able to identify actively transcribed genes in tissues representing down to 0.2% of the somatic cells in adult animals. Additionally, this method can be fully performed in a single laboratory by using third generation sequencing methods (ONT).

genetics↗