Biology subjects

Coussement, L.

Publications and source records attributed to Coussement, L..

4 recordsLinked to original sources

bioRxiv2026

Longitudinal dynamics of organ-specific proteomic aging clocks over a decade of midlife

Organ-specific proteomic clocks are promising tools for quantifying heterogeneity in biological aging, but their longitudinal behavior remains largely unexplored. Here, we analyzed paired plasma proteomic profiles with 10-year follow-up in middle-aged adults (n= 1,250) to evaluate their longitudinal properties. Cross-sectional associations of protein concentrations with age mirrored average longitudinal trajectories, validating the common cross-sectional training of clocks. Organ-specific age acceleration was moderately stable over the decade, and aging across organs progressed in parallel, with the immune and adipose systems acting as central hubs and early cardiorespiratory aging predicting downstream metabolic aging. Critically, longitudinal changes in predicted age tracked subclinical risk factor alterations. In women, the menopausal transition dominated the aging landscape and was associated with multi-organ age acceleration. Medication initiation altered clocks through specific drug-targeted proteins (such as renin and APOB) rather than generalized organ aging. Together, these findings position organ-specific proteomic clocks as interpretable, dynamic indicators of aging and organ health.

systems biology↗

bioRxiv2025

A transcriptional clock of the human pluripotency transition

Developmental timing differs strikingly between mammals. All embryonic and some placental lineages emerge from the pluripotent epiblast in a temporally defined sequence, lasting about two weeks in the human embryo, but only two days in mice. Moreover, the order of lineage segregation and gene expression differ between the species. We used human pluripotent stem cells to recapitulate this window of epiblast development in vitro. Simultaneous profiling of gene expression and chromatin accessibility in single cells revealed a robust, autonomous switch between cell states during this process. We reconstructed the integrative gene regulatory network (GRN) of transcription factors (TFs) and signalling molecules. Notably, this revealed a transcriptional cascade including temporally close positive and distant inhibitory connections. We suggest that this cascade acts as a transcriptional clock and governs the directionality, timing and intrinsic decisions during epiblast development. From individual gene interactions, we derived a mechanistic mathematical model of the transcriptional clock of pluripotency that closely reproduced gene expression dynamics and identified key regulatory connections. Moreover, our model revealed a bistable switch governing the transition, thus translating the GRN inference into an interpretable mechanism. Strikingly, the GRN model derived for humans predicted the acceleration of developmental timing in mice when initialised with mouse-specific expression patterns, yet still leading to a human-like expression state. Therefore, TF levels explain developmental timing, whereas the architecture of the network defines its trajectory. Together, our work provides novel conceptual insights into the intrinsic mechanisms of developmental transitions in the human embryo. HIGHLIGHTSO_LIThe human pluripotency transition is guided by an intrinsic developmental programme C_LIO_LIA cascade of transcription factors defines directionality and timing of the pluripotency transition through positive and negative interactions C_LIO_LITranscription factor levels explain developmental timing C_LIO_LIThe architecture of the gene regulatory network defines its trajectory C_LI GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/643129v1_ufig1.gif" ALT="Figure 1"> View larger version (37K): org.highwire.dtl.DTLVardef@1faf1aaorg.highwire.dtl.DTLVardef@10053borg.highwire.dtl.DTLVardef@1c76aacorg.highwire.dtl.DTLVardef@12c7b89_HPS_FORMAT_FIGEXP M_FIG C_FIG

developmental biology↗

bioRxiv2022

Liver transcriptomic and methylomic analyses identify transcriptional MAPK regulation in facultative hibernation of Syrian hamster

Hibernation consist of alternating torpor/arousal phases, during which animals cope with repetitive hypothermia and ischemia-reperfusion. Due to limited transcriptomic and methylomic information for facultative hibernators, we here conducted RNA and whole genome bisulfite sequencing in liver of hibernating Syrian hamster (Mesocricetus auratus). Gene Ontology analysis was performed on 844 differentially expressed genes (DEGs) and confirmed the shift in metabolic fuel utilization, inhibition of RNA transcription and cell cycle regulation as found in seasonal hibernators. We show a so far unreported suppression of MAPK and PP1 pathways. Notably, hibernating hamsters showed upregulation of MAPK inhibitors (DUSPs and SPRYs) and reduced levels of MAPK induced transcription factors. Promoter methylation was found to modulate the expression of genes targeted by these transcription factors. In conclusion, we document gene regulation between hibernation phases, which may aid the identification of pathways and targets to prevent organ damage in transplantation or ischemia-reperfusion.

genomics↗

bioRxiv2022

MAGE enables population level RNAseq driven genotyping and (differential) allelic divergence detection in healthy kidney and carcinoma

Decreasing sequencing costs have instigated large-scale RNAseq experiments, yet genetic polymorphisms in such data remain poorly exploited. Currently, allele-specific expression (ASE) studies focus almost exclusively on genetic variants explaining expression differences (cis-eQTLs), largely ignoring other ASE effects. The latter are typically associated with higher variance in expression of both copies of a gene, here called Allelic Divergence (AD). We therefore developed an RNAseq-driven population-level beta-binomial mixture model for (differential) AD detection. The model simultaneously enables RNAseq-driven genotyping, which outperforms alternative RNA genotyping methods when applied on healthy kidney data from The Cancer Genome Atlas. Moreover, we identify well-known non-cis-eQTL ASE, e.g. random monoallelic expression of HLA and immunoglobulin genes in healthy kidney, as well as allele-specific aberrations in clear cell kidney carcinoma, including long-range epigenetic silencing of protocadherins, copy-number alterations, and loss of imprinting. These methods are available as the Modeller of Allelic Gene Expression (MAGE) tool suite: https://biobix.github.io/MAGE/.

bioinformatics↗