Biology subjects

Perez-Garcia, V.

Publications and source records attributed to Perez-Garcia, V..

5 recordsLinked to original sources

bioRxiv2026

Full-thickness spatial transcriptomics of the human uterus reveals basalis niche architecture and regeneration gradients during menstrual breakdown

The human endometrium (uterine lining) undergoes cyclical breakdown and scarless regeneration during each menstrual cycle, representing an exceptional model of adult tissue renewal. Regeneration is driven primarily by progenitor cells retained within the deep, basalis compartment during menstruation, yet the full-depth spatiotemporal dynamics of this process have remained understudied due to anatomical and technical limitations. Here, we map spatial gene-expression gradients across the full thickness of the human endometrium, from the myometrial-endometrial boundary to the luminal surface, using high-resolution spatial transcriptomics integrated with single-cell transcriptomics. We profile more than ten million cells from biopsies, hysterectomy samples and menstrual fluid, enriching for the menstrual and proliferative phases, which are underrepresented in previous studies. We show that endometrial breakdown, regeneration and rapid luminal re-epithelialisation are concurrent rather than temporally separated, organised across distinct tissue compartments, revealing a mode of tissue renewal in which shedding and repair operate simultaneously. Continuous basalis-to-luminal transcriptional gradients link progenitor identity, niche signalling, and tissue remodelling, defining a coordinated regenerative axis spanning the full tissue depth. We resolve the basalis epithelial niche at unprecedented molecular resolution, identifying for the first time a discrete, predominantly quiescent progenitor-like epithelial subset and specialised supporting SFRP5+ fibroblasts, both characterised by WNT inhibition, alongside lymphoid aggregates, forming a multi-component architecture that persists after menopause, consistent with a long-lived regenerative reservoir. Together, these findings establish spatial transcriptional gradients as a central organising principle of endometrial renewal, providing a molecular framework for understanding disorders of menstruation, implantation failure, and impaired tissue repair.

cell biology↗

bioRxiv2026

Hormonally responsive bovine oviductal organoids recapitulate native oviductal secretions and enhance sperm capacitation

The oviduct provides the dynamic microenvironment that supports fertilization and early embryo development yet replicating its hormonally regulated secretory activity in vitro remains a major challenge. Here, we established bovine oviductal epithelial organoids that reproduce the structural polarity and endocrine responsiveness of the native oviduct. Exposure to either estradiol or progesterone resulted in distinct transcriptomic and proteomic landscapes that were characteristic of the follicular and luteal phases, respectively. This included the upregulation of canonical phase-specific markers, such as OVGP1, NTS, HP and TGM2. Proteomic profiling of organoid-derived secretions (ODS) revealed extensive overlap with in vivo oviductal fluid. Integration of transcriptomic and proteomic datasets by multi-omics factor analysis identified coherent biological signatures defining each hormonal state. Functionally, ODS obtained from estradiol-treated organoids enhanced sperm capacitation and acrosome reaction, recapitulating the activity of follicular-phase oviductal fluid. These findings demonstrate that hormonally responsive oviductal organoids generate bioactive secretions that emulate the molecular and functional features of the native oviductal environment, providing a sustainable and physiologically relevant platform for studying gamete-maternal communication and improving assisted reproduction technologies.

developmental biology↗

bioRxiv2025

EGFR-Driven Phenotypes Dictate Differential Therapeutic Response to Radiotherapy and Temozolomide in Glioblastoma.

Despite the established Stupp regimen, glioblastoma (GBM) remains a highly lethal cancer with a 5-year survival rate below 10%. The epidermal growth factor receptor (EGFR) is frequently amplified or mutated in GBM, and we have previously shown that different EGFR statuses correlate with distinct tumor phenotypes and responses to temozolomide (TMZ). In this study, we investigated the differential response of two mouse GBM models, one overexpressing EGFRwt (EGFRwt/amp) and the other with overexpressing the EGFRvIII variant, to radiotherapy (RT) alone and in combination with TMZ. While both tumor models were sensitive to RT in vitro, in vivo experiments showed no significant survival benefit from RT for mice carrying EGFRwt/amp GBM, regardless of the RT schedule. Moreover, for these tumors, different combinations of RT with TMZ were not significantly better than spaced TMZ treatment alone. In contrast, EGFRvIII tumors responded well to RT alone, and spacing out the RT doses offered no additional benefit. Although a Stupp-like protocol provided a small benefit compared to RT alone in this model, the combinatorial treatment also induced the expression of several resistance markers, such as MGMT or NF-{kappa}b phosphorylation. Our retrospective analysis of patient data supports these findings, suggesting that RT alone may not improve survival for patients with EGFRwt/amp GBM, whereas for GBM with EGFRvIII mutations, adding RT or TMZ and RT, does provide a clear survival benefit to surgery or to surgery and RT, respectively. These results suggest that EGFR status could serve as a crucial biomarker to predict tumor response and guide personalized treatment decisions, particularly in cases where minimizing toxicity is a priority.

cancer biology↗

bioRxiv2020

BAP1/ASXL complex modulation regulates Epithelial-Mesenchymal Transition during trophoblast differentiation and invasion

Normal function of the placenta depends on the earliest developmental stages when trophoblast cells differentiate and invade into the endometrium to establish the definitive maternal-fetal interface. Previously, we identified the ubiquitously expressed tumour suppressor BRCA1-associated protein 1 (BAP1) as a central factor of a novel molecular node controlling early mouse placentation. However, functional insights into how BAP1 regulates trophoblast biology are still missing. Using CRISPR/Cas9 knockout and overexpression technology, here we demonstrate that the downregulation of BAP1 protein is essential to trigger epithelial-mesenchymal transition (EMT) during trophoblast differentiation associated with a gain of invasiveness. This function, which is conserved in mouse and humans, is dependent on the binding of BAP1 binding to Additional sex comb-like (ASXL1/2/3) proteins to form the Polycomb repressive deubiquitinase (PR-DUB) complex. Our results reveal that the physiological modulation of BAP1 determines the invasive properties of trophoblast, delineating a new role of the BAP1 PR-DUB complex in regulating early placentation.

developmental biology↗

bioRxiv2018

Fetal and trophoblast PI3Kp110α have distinct roles in regulating resource supply to the growing fetus

Previous studies suggest that the placental supply of nutrients to the fetus adapts according to fetal demand. However, the signaling events underlying placental adaptations remain largely unknown. Earlier work in mice has revealed that loss of the phosphoinositide 3-kinase p110 impairs feto-placental growth but placental nutrient supply is adaptively increased. Here we explore the role of p110 in the epiblast-derived (fetal) and trophoblast lineages of the conceptus in relation to feto-placental growth and placental development and transfer function. Using conditional gene manipulations to knock-down p110 either by [~]50% or [~]100% in the fetal lineages and/or trophoblast, this study shows that p110 in the fetus is essential for prenatal development and a major regulator of placental phenotype in mice. Complete loss of fetal p110 caused embryonic death, whilst heterozygous loss resulted in fetal growth restriction and impaired placental formation and nutrient transport. Loss of trophoblast p110 also resulted in abnormal placental development, although fetuses were viable. However, in response to complete loss of trophoblast p110, the placenta failed to transport sufficient amino acid to match fetal demands for growth. Using RNA-seq, we identified several genes downstream of p110 in the trophoblast that are important in adapting placental phenotype to support fetal growth. Further work using CRISPR/Cas9 genome targeting showed that loss of p110 differentially affects the expression of genes in trophoblast and embryonic stem cells. Our findings thus reveal important, but distinct roles for p110 signaling in the different compartments of the conceptus, which control fetal resource acquisition and ultimately affect healthy growth.\n\nOne Sentence SummaryFetal and trophoblast p110 modify resource allocation

developmental biology↗