Biology subjects

Sakoparnig, T.

Publications and source records attributed to Sakoparnig, T..

3 recordsLinked to original sources

bioRxiv2025

Choroid plexus sex differences in secretory signalling and immune compartments

The choroid plexus (ChP)-cerebrospinal fluid (CSF) axis is emerging as a key regulator of the brain environment. The ChP is a multi-functional structure, which forms the blood-CSF barrier, and acts as a sensor of inputs from the periphery and the brain, dynamically responding by modulating its secretome into the CSF. However, sex differences in the ChP have been little explored. Molecular profiling of the adult mouse ChP at the transcriptomic and proteomic levels revealed sex differences across multiple cell types, with immune signatures enriched in females. Interestingly, border associated macrophages showed distinct sex differences in the stromal and epiplexus compartments. We further uncovered sex differences in ChP secretory signalling, with functional differences between males and females. Finally, the human LVChP showed largely similar sex differences. Together, our findings highlight that sex differences may play an important role in ChP function in both health and disease.

neuroscience↗

bioRxiv2020

RNA-bound PGC-1α controls gene expression in liquid-like nuclear condensates

The peroxisome-proliferator-activated receptor-{gamma} coactivator-1 (PGC-1) integrates environmental cues by controlling complex transcriptional networks in various metabolically active tissues. However, it is unclear how a transcriptional coregulator coordinates dynamic biological programs in response to multifaceted stimuli such as endurance training or fasting. Here, we discovered a central function of the poorly understood C-terminal domain (CTD) of PGC-1 to bind RNAs and assemble multi-protein complexes. Surprisingly, in addition to controlling the coupling of transcription and processing of target genes, RNA binding is indispensable for the recruitment of PGC-1 to chromatin into liquid-like nuclear condensates, which compartmentalize and regulate active transcription. These results demonstrate a hitherto unsuspected molecular mechanism by which complexity in the regulation of large transcriptional networks by PGC-1 is achieved. These findings are not only essential for the basic understanding of transcriptional coregulator-driven control of biological programs, but will also help to devise new strategies to modulate these processes in pathological contexts in which PGC-1 function is dysregulated, such as type 2 diabetes, cardiovascular diseases or skeletal muscle wasting.

molecular biology↗

bioRxiv2019

Whole genome phylogenies reflect long-tailed distributions of recombination rates in many bacterial species

Although homologous recombination is accepted to be common in bacteria, so far it has been challenging to accurately quantify its impact on genome evolution within bacterial species. We here introduce methods that use the statistics of single-nucleotide polymorphism (SNP) splits in the core genome alignment of a set of strains to show that, for many bacterial species, recombination dominates genome evolution. Each genomic locus has been overwritten so many times by recombination that it is impossible to reconstruct the clonal phylogeny and, instead of a consensus phylogeny, the phylogeny typically changes many thousands of times along the core genome alignment. We also show how SNP splits can be used to quantify the relative rates with which different subsets of strains have recombined in the past. We find that virtually every strain has a unique pattern of frequencies with which its lineages have recombined with those of other strains, and that the relative rates with which different subsets of strains share SNPs follow long-tailed distributions. Our findings show that bacterial populations are neither clonal nor freely recombining, but structured such that recombination rates between different lineages vary along a continuum spanning several orders of magnitude, with a unique pattern of rates for each lineage. Thus, rather than reflecting clonal ancestry, whole genome phylogenies reflect these long-tailed distributions of recombination rates.

evolutionary biology↗