Biology subjects

Ripoll-Cladellas, A.

Publications and source records attributed to Ripoll-Cladellas, A..

4 recordsLinked to original sources

bioRxiv2026

Federated single-cell QTL meta-analysis reveals novel disease mechanisms

Genetic effects on gene expression are often cell type-specific and obscured in bulk analyses. To resolve this context-dependent regulation, we performed a federated cis-eQTL meta-analysis across 12 PBMC datasets (2,032 individuals, 2.5 million cells). Across six immune cell types, we identified cis-eQTLs for 6,592 genes and fine-mapped 14,985 independent loci. Notably, the 42% of eQTLs that were undetected in a bulk eQTL study on 43,301 whole blood samples also showed stronger enrichment for disease GWAS loci. We further identified three genome-wide significant and 65 suggestive loci affecting the abundance of (rare) immune cell types and validated these using previously reported hematological GWAS and bulk-derived trans-eQTLs. Integrating single-cell cis-eQTLs with bulk trans-eQTLs enabled us to anchor 6,382 trans-eGenes (37.2% novel) to upstream regulators and reconstruct directed gene regulatory relationships. For example, a hemorrhoidal disease-associated variant showed a CD4+ T cell-specific cis-eQTL on BACH1 that colocalized with 45 immune and metabolic trans-eGenes. These results demonstrate the power of single-cell QTL meta-analysis in interpreting complex trait genetics.

genetics↗

bioRxiv2025

Multimodal data analysis reveals asynchronous aging dynamics across female reproductive organs

Female reproductive aging is a complex process with profound systemic health implications, yet the molecular and structural dynamics of aging across reproductive organs and tissues remain largely unexplored. Here, we integrate deep learning-based analysis of 1,112 histological images with RNA-seq data from 659 samples across seven reproductive organs in 304 female donors aged 20-70 years. We show that female reproductive organs and tissues have asynchronous aging dynamics: while the ovary and vagina age gradually, the uterus undergoes an abrupt transcriptional and cellular transition around the age of menopause. Tissue segmentation highlights that the myometrium in the uterine wall is the most age-affected tissue, marked by extracellular matrix remodeling and immune activation. Across reproductive organs, the epithelial tissue is also strongly affected by age, with the vaginal epithelium showing a unique sharp menopausal transition. Integration via multi-omics factor analysis links these tissue-specific histological transformations to specific molecular shifts, many with nonlinear expression trajectories and enriched in heritable reproductive traits such as pelvic organ prolapse and age at menarche. These findings position menopause as a key inflection point in female aging and provide insights with tissue-specific focus to support healthier menopausal transitions and reduce age-related disease risk.

genomics↗

bioRxiv2024

Single-cell atlas of the human immune system reveals sex-specific dynamics of immunosenescence

Immunosenescence, or immune aging, is characterized by both changes in cell type abundance and a decline in cellular function, leading to increased susceptibility to immune-related diseases. Yet, the extent to which sex influences the dynamic composition of immune cells during immunosenescence remains unknown. Here, we use single-cell RNA sequencing in peripheral blood mononuclear cells from 982 donors to uncover the sex-specific immune aging dynamics. We reveal that aging drives sexually dimorphic compositional and transcriptional shifts, with females showing stronger immune remodeling. Female-specific shifts include the expansion of three cytotoxic CD8+ T effector memory subpopulations and inflammatory monocytes. In addition, female CD4+ central memory T cells exhibit abundance shifts in subpopulations involved in autoimmunity alongside age-associated transcriptional signatures enriched for autoimmune-related pathways. Conversely, males show an age-related expansion of a B cell subpopulation associated with an asymptomatic precursor state to chronic lymphocytic leukemia. These sex-biased, functionally distinct immune subpopulations represent sex-specific hallmarks of immune aging. Our work underscores the complexity and sexual dimorphism of immunosenescence and supports the development of sex-specific strategies to promote healthy aging. Highlights- A single-cell transcriptomic atlas of >1 million PBMCs from 982 donors uncovers sex-specific immune aging trajectories. - Aging females show greater cellular remodeling and stronger transcriptional shifts than males. - Female-specific expansions with age of cytotoxic CD8+ T effector memory cells, inflammatory monocytes, and CD4+ T helper 22 cells reflect a systemic shift toward a pro-inflammatory, self-reactive immune state. - Male-specific B cell shifts reveal expansion of CD5+ clonal subpopulations linked to leukemic precursor states. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=158 SRC="FIGDIR/small/622096v2_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@161b6b1org.highwire.dtl.DTLVardef@214d55org.highwire.dtl.DTLVardef@5c3ee8org.highwire.dtl.DTLVardef@263227_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗

bioRxiv2021

Genetic, parental and lifestyle factors influence telomere length

The average length of telomere repeats (TL) declines with age and is considered to be a marker of biological ageing. Here, we measured TL in six blood cell types from 1,046 individuals using the clinically validated Flow-FISH method. We identified remarkable cell-type-specific variations in TL. Host genetics, environmental, parental and intrinsic factors such as sex, parental age, and smoking are associated to variations in TL. By analysing the genome-wide methylation patterns, we identified that the association of maternal, but not paternal, age to TL is mediated by epigenetics. Coupling these measurements to single-cell RNA-sequencing data for 62 participants revealed differential gene expression in T-cells. Genes negatively associated with TL were enriched for pathways related to translation and nonsense-mediated decay. Altogether, this study addresses cell-type-specific differences in telomere biology and its relation to cell-type-specific gene expression and highlights how perinatal factors play a role in determining TL, on top of genetics and lifestyle.

cell biology↗