Biology subjects

Zapparoli, E.

Publications and source records attributed to Zapparoli, E..

3 recordsLinked to original sources

bioRxiv2026

Novel role of the lncRNA EPR as oncosuppressor in intestinal cancer.

We previously reported that the murine lncRNA Epr is essential for maintaining colon mucosal integrity and permeability. Mice lacking Epr in the colon are more susceptible to colitis and tumor development. Additionally, we demonstrated that human EPR expression is reduced in ulcerative colitis and in a small cohort of colon adenocarcinoma patients. Here, we present evidence that human and mouse EPR share several key physiological features: preferential binding to the KH1 domain of their interacting protein, KSRP; specific expression in canonical and immature goblet cells of the large intestine; and a functional role in intestinal goblet cell development. The correlation between EPR levels and survival in large cohorts of metastatic colon adenocarcinoma patients, together with the capacity of human EPR to inhibit cell proliferation and induce apoptosis in two distinct human colon adenocarcinoma cell lines, suggests that EPR may serve as both a valuable prognostic marker for goblet cell-derived adenocarcinomas and a potential therapeutic target.

cancer biology↗

bioRxiv2026

Effects of introgressed Neanderthal alleles on present-day brain morphology

Neanderthal introgression contributed a small fraction of genetic variants to present-day non-African genomes. While differences in cranial globularity between Neanderthal and modern humans are well documented from endocasts, the phenotypic consequences of these introgressed alleles can illuminate otherwise inaccessible genetically divergent brain structures. We analyzed 370 MRI-derived brain traits--including cortical and subcortical regional measurements, cortical folding metrics, diffusion tracts--in nearly 40,000 UK Biobank participants. To quantify the impact of Neanderthal ancestry, we intersected trait-associated loci with Neanderthal-derived variants identified from introgressed segments imputed in the same subjects. Low-frequency introgressed variants were depleted for detectable effects on brain phenotypes, whereas common introgressed variants showed no comparable depletion. Conversely, Neanderthal deserts were consistently enriched for functional effects. Eight associations were fine-mapped to Neanderthal-derived variants: one locus near the gene DAAM1 was especially prominent across multiple traits, including opposite effects in the cuneus and precuneus mediated by introgressed regulatory variants. Genome-wide directional alignment of Neanderthal effects was limited but became evident when focusing on suggestive loci: frontal and parietal areas were the most consistently affected traits, though not in a direction that obviously mirrors known modern-archaic morphology divergence. Several of these loci also influenced neuropsychiatric traits, with detectable polygenic consequences against schizophrenia and towards major depression, linking neuroanatomical and neuropsychiatric impact of Neanderthal introgression. These findings suggest that while introgressed alleles affecting divergent neuroanatomy between modern humans and Neanderthals were largely purged, a subset of tolerated alleles continues to shape human brain morphology and mental health.

genomics↗

bioRxiv2025

Imputed transcriptional patterns in ancient genomes reveal molecular targets of selection

The genetically regulated component of molecular traits can be imputed from ancient genomes, though low genotyping quality and genetic drift may impair accurate expression prediction and results interpretation. We developed tissue-specific gene expression and alternative splicing prediction models and applied them to over a thousand imputed ancient genomes spanning 10,000 years of Western Eurasian history. We revealed gene regulatory patterns diverging with time, space and genomic ancestry by fitting predicted transcriptional profiles onto multivariable models including these factors. By interpreting associations with time as recent natural selection we identify hits mediated by transcriptional changes. Finally, we fine-mapped these selection signals to tissue-specific transcriptional traits, explicitly accounting for prediction uncertainty. Among others, we elucidate the spatial patterns and the regulatory features promoting selection at LCT, FADS1, SLC22A5/P4HA2, ACAD10/OAS3 and find novel signals of selection at TBIMB6, SORD2P and AC012370.3.

genomics↗