Biology subjects

Notario Manzano, R.

Publications and source records attributed to Notario Manzano, R..

4 recordsLinked to original sources

bioRxiv2025

Whole-genome methylation profiling of menstrual stem cells identifies novel biomarkers for endometriosis

Endometriosis, despite its high prevalence, is underdiagnosed and poorly managed due to lack of clinically validated biomarkers and pathophysiological insight. Menstrual blood-derived stem cells (MenSCs) have been implicated in disease pathogenesis, but their diagnostic potential remains unexplored. We conducted a clinical study (n=42; 19 endometriosis, 23 controls) to assess whether DNA methylation profiles of freshly isolated MenSCs can identify disease-specific biomarkers. Whole-genome methylation sequencing revealed differentially methylated regions (DMRs) enriched in genes linked to hallmarks of endometriosis (e.g., inflammation, tissue remodelling, development). These DMRs robustly distinguished cases from controls, independent of technical and clinical variables. Machine learning models trained and validated on these DMRs achieved high diagnostic performance (specificity 83%, sensitivity 79%). Integration with an independent single-cell RNA sequencing dataset showed that the DMRs may modulate gene expression, further supporting their biological relevance. These findings position MenSC DNA methylation profiling as a promising, non-invasive approach for early endometriosis diagnosis and personalised care.

molecular biology↗

bioRxiv2025

N-Cadherin/α-Catenin Drive Adhesion and Actin Regulation to Orchestrate Tunneling Nanotube Formation

Cell-to-cell communication is essential for maintaining homeostasis in multicellular organisms. Tunneling nanotubes (TNTs)--actin-based membranous connections--mediate the exchange of diverse cargoes between distant cells. Unlike other cellular protrusions, TNTs exhibit unique ultrastructural features and are enriched in the adhesion molecule N-Cadherin. Here, we dissect the role of N-Cadherin in the formation and function of TNTs in SH-SY5Y human neuronal-like cells. We show that N-Cadherin, via its effectors -Catenin and p120-Catenin, is a central regulator of TNT architecture and their cargo transfer capability. Regulators of cortical tension p120-Catenin, ROCK, and non-muscle myosin II also emerge as critical for TNT functionality, highlighting a mechanosensitive component to TNT regulation. Moreover, we reveal that NMIIA can be processive inside TNTs and transfer through them using actins retrograde flow. Finally, we identify the Cdc42-IRSp53-N-WASP pathway as a downstream effector axis enhancing intercellular transfer downstream of N-Cadherin. Together, our findings uncover a structural and functional link between N-Cadherin signaling and TNT-mediated intercellular communication.

cell biology↗

bioRxiv2023

N-Cadherin and alpha-catenin regulate formation of functional tunneling nanotubes

Cell-to-cell communication it is a fundamental mechanism by which unicellular and multicellular organisms maintain relevant functions as development or homeostasis. Tunneling nanotubes (TNTs) are a type of contact-mediated cell-to-cell communication defined by being membranous structures based on actin that allow the exchange of different cellular material. TNTs have been shown to have unique structural features compared with other cellular protrusions and to contain the cell adhesion molecule N-Cadherin. Here, we investigated the possible role of N-Cadherin and of its primary linker to the actin cytoskeleton, -Catenin in regulating the formation and transfer function of TNTs. Our data indicate that N-Cadherin through its downstream effector -Catenin is a major regulator of TNT formation, ultrastructure, as well as of their ability to transfer material to other cells.

cell biology↗

bioRxiv2022

Proteomic landscape of tunneling nanotubes reveals CD9 and CD81 tetraspanins as key regulators

Tunneling nanotubes (TNTs) are open actin- and membrane-based channels, connecting remote cells and allowing direct transfer of cellular material (e.g. vesicles, mRNAs, protein aggregates) from cytoplasm to cytoplasm. Although they are important especially in pathological conditions (e.g., cancers, neurodegenerative diseases), their precise composition and their regulation were still poorly described. Here, using a biochemical approach allowing to separate TNTs from cell bodies and from extracellular vesicles and particles (EVPs), we obtained the full composition of TNTs compared to EVPs. We then focused to two major components of our proteomic data, the CD9 and CD81 tetraspanins, and further investigated their specific roles in TNT formation and function. We show that these two tetraspanins have distinct non-redundant functions: CD9 participates in stabilizing TNTs, whereas CD81 expression is required to allow the functional transfer of vesicle in the newly formed TNTs, possibly by regulating docking to or fusion with the opposing cell.

cell biology↗