Biology subjects

Calvo-Asensio, I.

Publications and source records attributed to Calvo-Asensio, I..

3 recordsLinked to original sources

bioRxiv2025

Ly6d expression delineates two putative postnatal thymus epithelial progenitor cells that are differentially affected by ageing

The thymus is a primary lymphoid organ which provides essential structural and functional support for the development of naive T cells. Thymic epithelial cells (TECs), key components of the thymic stroma, are classified into cortical (cTEC) and medullary (mTEC) lineages based on their distinct molecular, structural, transcriptional, and functional characteristics. Advances in single-cell RNA sequencing (scRNA-seq) have revealed significant TEC heterogeneity, including the identification of intertypical TECs that share properties of both cTEC and mTEC and have been postulated to play a role in the development and maintenance of thymic function. To date, the identity and maintenance of postnatal TEPCs remain unclear, with debates on whether bipotent TEPCs persist after birth or if lineage-restricted progenitors independently maintain TEC compartments. Using an inducible lineage-tracing system based on {beta}5t expression, we explored the early dynamics of the relationships between TEPC and mTEC progenitors and their progeny. Our results identified two potential lineage-biassed TEPC subpopulations, distinguished by Ly6d expression. Additionally, we observed that ageing disproportionately affects Ly6d-compared to Ly6d+ TEPCs, with implications for the rejuvenation of the ageing thymic epithelium. This study provides insights into the developmental pathways of TEC lineages and their maintenance, contributing to strategies for enhancing thymic function in ageing and disease.

immunology↗

bioRxiv2022

Combined multidimensional single-cell protein and RNA profiling dissects the cellular and functional heterogeneity of thymic epithelial cells

The network of thymic stromal cells provides essential niches with unique molecular cues controlling T-cell development and selection. Recent single-cell RNA-sequencing studies uncovered a large transcriptional heterogeneity among thymic epithelial cells (TEC) demonstrating a previously unappreciated complexity. However, there are only very few cell markers that allow a comparable phenotypic identification of TEC. Here we deconvoluted by massively parallel flow cytometry and machine learning known and novel TEC phenotypes into novel subpopulations and related these by CITEseq to the corresponding TEC subtypes defined by the cells individual RNA profiles. This approach phenotypically identified perinatal cTEC, physically located these cells within the cortical stromal scaffold, displayed their dynamic change during the life course and revealed their exceptional efficiency in positively selecting immature thymocytes. Collectively, we have identified novel markers that allow for an unprecedented dissection of the thymus stromal complexity, the cells physical isolation and assignment of specific functions to individual TEC subpopulations.

immunology↗

bioRxiv2020

Ageing compromises mouse thymus function and remodels epithelial cell differentiation

Ageing is characterised by cellular senescence, leading to imbalanced tissue maintenance, cell death and compromised organ function. This is first observed in the thymus, the primary lymphoid organ that generates and selects T cells. However, the molecular and cellular mechanisms underpinning these ageing processes remain unclear. Here, we show that mouse ageing leads to less efficient T cell selection, decreased self-antigen representation and increased T cell receptor repertoire diversity. Using a combination of single-cell RNA-seq and lineage-tracing, we find that progenitor cells are the principal targets of ageing, whereas the function of mature thymic epithelial cells is compromised only modestly. Specifically, an early-life precursor cell population, retained in the mouse cortex postnatally, is virtually extinguished at puberty. Concomitantly, a medullary precursor cell quiesces, thereby impairing maintenance of the medullary epithelium. Thus, ageing disrupts thymic progenitor differentiation and impairs the core immunological functions of the thymus.

immunology↗