Biology subjects

Seraphin, R.

Publications and source records attributed to Seraphin, R..

2 recordsLinked to original sources

bioRxiv2026

Genetic determinism and inheritance of differential DNA methylation profiles across three successive generations in quail.

Environmental exposures can induce epigenetic modifications that persist across generations, potentially contributing to the transmission of environmentally-induced phenotypes. However, the extent to which such persistence of molecular changes are maintained independently of genetic mechanisms remains unclear. In this study, we investigated the evolution and genetic determinism of DNA methylation (DNAm) variation across three successive generations of Japanese quails (G0 to G2) belonging to two epilines, defined according to whether their female ancestor had received genistein supplementation (epi+) or not (epi-). Using reduced representation bisulfite sequencing (RRBS), we characterised CpG methylation patterns and identified differentially methylated cytosines (DMCs) and regions (DMRs) between control and genistein-supplemented epilines. Out of 112,745 CpG sites analysed, no DMCs or DMRs were detected between epilines in the first generation following exposure (G0), whereas 621 DMCs (36 DMRs) were identified in G1, and 1,381 DMCs (101 DMRs) in G2. Despite this progressive increase of differential methylation sites, mean differences in methylation rate between epilines were globally small. Similarly, genome-wide genetic differentiation between epilines was very limited. Overall, SNP-based heritability of DNA methylation was 0.19 indicating that genetic variation accounted for only a small part of the global variation of DNAm levels. By contrast, DNAm at differentially methylated CpG sites was extensively under genetic control, with a mean SNP-based heritability > 0.5, and meQTL analysis further identified significant associations between SNPs and methylation levels. Together, these results indicate that local DNAm differentiation in quail is under substantial genetic regulation, while the limited genetic differentiation between groups suggests that genetic variation alone can not fully explain the progressive accumulation of methylation differences following an ancestral exposure to genistein. These results support DNAm as a plausible molecular candidate mechanism in the multigenerational response to environmental exposure and highlight the complex interplay between genetic and epigenetic regulations in the inheritance of phenotypes.

genomics↗

bioRxiv2022

Evidence for close molecular proximity between reverting and undifferentiated cells

According to Waddingtons epigenetic landscape concept, the differentiation process can be illustrated by a cell akin to a ball rolling down from the top of a hill (proliferation state) and crossing furrows before stopping in basins or "attractor states" to reach its stable differentiated state. However, it is now clear that some committed cells can retain a certain degree of plasticity and reacquire phenotypical characteristics of a more pluripotent cell state. In line with this dynamic model, we have previously shown that differentiating cells (chicken erythrocytic progenitors (T2EC)) retain for 24 hours the ability to self-renew when transferred back in self-renewal conditions. Despite those intriguing and promising results, the underlying molecular state of those "reverting" cells remains unexplored. The aim of the present study was therefore to molecularly characterize the T2EC reversion process by combining advanced statistical tools to make the most of single cell transcriptomic data. For this purpose, T2EC, initially maintained in a self-renewal medium (0H), were induced to differentiate for 24h (24H differentiating cells); then a part of these cells was transferred back to the self-renewal medium (48H reverting cells) and the other part was maintained in the differentiation medium for another 24h (48H differentiating cells). For each time point, cell transcriptomes were generated using scRT-qPCR and scRNAseq. Our results showed a strong overlap between 0H and 48H reverting cells when applying dimensional reduction. Moreover, the statistical comparison of cell distributions and differential expression analysis indicated no significant differences between these two cell groups. Interestingly, gene pattern distributions highlighted that, while 48H reverting cells have gene expression pattern more similar to 0H cells, they retained traces of their engagement in the differentiation process. Finally, Sparse PLS analysis showed that only the expression of 3 genes discriminates 48H reverting and 0H cells. Altogether, we show that reverting cells return to an earlier molecular state almost identical to undifferentiated cells and demonstrate a previously undocumented physiological and molecular plasticity during the differentiation process, which most likely results from the dynamic behavior of the underlying molecular network.

cell biology↗