Biology subjects

Bourillot, P.-Y.

Publications and source records attributed to Bourillot, P.-Y..

3 recordsLinked to original sources

bioRxiv2025

A STAT3-regulated lncRNA integrates microRNA biogenesis and sequestration to safeguard naive pluripotency

Leukemia inhibitory factor (LIF)/STAT3 signaling is central to maintaining naive pluripotency in mouse embryonic stem cells (mESCs). We identify Asgard, a previously uncharacterized long non-coding RNA, as a direct STAT3 target required for efficient self-renewal. Asgard is rapidly induced by LIF, enriched in the epiblast, and its depletion reduces alkaline phosphatase-positive colony formation while enhancing differentiation. Mechanistically, Asgard fulfils a dual role: it acts as the primary transcript for the differentiation-promoting microRNA Odin, while also functioning as a sponge to sequester Odin and related miRNAs. This dual mechanism enables Asgard to both generate and buffer pro-differentiation signals, thereby stabilizing the pluripotent state while preserving responsiveness to lineage cues. Our work reveals a new paradigm in RNA-mediated control of stem cell identity, where a single STAT3-regulated lncRNA couples microRNA production with competitive inhibition to safeguard naive pluripotency.

developmental biology↗

bioRxiv2025

Identification of novel candidate regulators of human naive pluripotency by means of a genetic switch utilizing the chimeric receptor G-CSFR:GP130

This study investigated the molecular mechanisms underpinning the transition from primed to naive pluripotency in human pluripotent stem cells (hPSCs) by utilizing a dual genetic switch combining hormone-dependent STAT3-ERT2 and a chimeric GCSFR:gp130 receptor. Upon activation with tamoxifen and G-CSF, hPSCs demonstrated upregulation of naive markers, and sustained self-renewal independent of LIF. Transcriptomic analyses revealed distinct clusters of early response genes, with a subset of 26 genes significantly enriched in the human epiblast. Knockdown experiments further delineated essential regulators that modulate differentiation and proliferation during naive reprogramming including interferon gamma inducible protein (IFI)16 and interferon-induced transmembrane (IFITM) proteins. Moreover, functional assays using mutant chimeric GCSFR:gp130 receptor highlighted the critical role of JAK kinase recruitment in orchestrating epigenomic remodeling and early gene activation. This approach establishes a robust platform to dissect the signaling dynamics governing the accession of hPSCs to naive pluripotency.

cell biology↗

bioRxiv2019

Regulation of Cyclin E by transcription factors of the naïve pluripotency network in mouse embryonic stem cells

Continuous, non-cell cycle-dependent expression of cyclin E is a characteristic feature of mouse embryonic stem cells (ESCs). We studied the 5 regulatory region of Cyclin E, also known as Ccne1, and identified binding sites for transcription factors of the naive pluripotency network, including Esrrb, Klf4, and Tfcp2l1 within 1 kilobase upstream of the transcription start site. Luciferase assay and chromatin immunoprecipitation-quantitative polymerase chain reaction (ChiP-qPCR) study highlighted one binding site for Esrrb that is essential to transcriptional activity of the promoter region, and three binding sites for Klf4 and Tfcp2l1. Knockdown of Esrrb, Klf4, and Tfcp2l1 reduced Cyclin E expression whereas overexpression of Esrrb and Klf4 increased it, indicating a strong correlation between the expression level of these factors and that of cyclin E. We observed that cyclin E overexpression delays differentiation induced by Esrrb depletion, suggesting that cyclin E is an important target of Esrrb for differentiation blockade. We observed that mESCs express a low level of miR-15a and that transfection of a miR-15a mimic decreases Cyclin E mRNA level. These results lead to the conclusion that the high expression level of Cyclin E in mESCs can be attributed to transcriptional activation by Esrrb as well as to the absence of its negative regulator, miR-15a.

cell biology↗