Biology subjects

Vincelle-Nieto, A.

Publications and source records attributed to Vincelle-Nieto, A..

4 recordsLinked to original sources

bioRxiv2025

Single-cell multiomics reveals epigenetic rewiring of splenic memory B cells during murine malaria reinfection

Malaria induces slow, gradually acquired, non-sterilizing immunity whose cellular and regulatory underpinnings remain incompletely understood. Here, we combine a sequential Plasmodium yoelii 17XNL infection model in BALB/c mice, in which primary parasitemia resolves spontaneously and confers robust protection upon homologous reinfection, with single-cell RNA and chromatin accessibility profiling to dissect how primary infection and recall reshape splenic immunity, with a focus on B cells. We generate a multiomic atlas of >50,000 splenic mononuclear cells, resolving thirteen major immune lineages and 48 subpopulations, and show that B cells dominate the response and diversify into naive/mature, germinal center, memory, and plasmablast compartments. Trajectory analysis reveals distinct differentiation paths towards germinal center, memory, and mature B cells, and uncovers infection-dependent shifts in transcription factor activity, cis-regulatory element usage, and gene regulatory networks. Reinfection is associated with a shift in memory B-cell composition and transcriptional programs towards extrafollicular-like, IgM- conventional memory B cells together with epigenetic modules linked to rapid antibody production. Together, these data provide a systems-level view of B cell plasticity in experimental malaria and provides a mechanistic framework from a highly protective P. yoelii reinfection model with implications for understanding non-sterilizing immunity in endemic settings.

genomics↗

bioRxiv2025

Cyclophosphamide chemotherapy induces early p53-directed cytotoxic gene expression changes in ovarian gonadotoxicity

The alkylating chemotherapeutic cyclophosphamide (CPA) is gonadotoxic, commonly resulting in depletion of ovarian primordial follicles and leading to infertility and premature menopause in female cancer patients. However, the mechanisms underlying the early stages of CPA-induced ovarian damage are unclear, limiting our ability to prevent gonadotoxicity. This study provides a comprehensive temporal exploration of the transcriptomic profiles of ex vivo intact mouse ovaries exposed to CPA. Analyses of CPA responses from 8 to 36 hours revealed an important early role of p53 signaling. Bioinformatic analyses showed early increases in expression of specific gene clusters associated with apoptosis, DNA damage responses, and cell cycling, while expression of autophagy-associated genes was decreased. Several transcription factors, including E2F family members, likely drive early apoptosis-induced damage and p53 pathway activation. These findings provide mechanistic insight into CPA-induced ovarian toxicity, providing new avenues for the development of protective interventions.

pharmacology and toxicology↗

bioRxiv2024

Purinergic Receptor P2Y13 Controls Activation and Mode of Division in Subependymal Adult Neural Stem Cells

The subependymal zone (SEZ) of the mammalian brain is the most active germinal area that continues to generate newborn neurons throughout life. This area harbors a population of neural stem cells (NSCs) that can be found in different states of activation, each differing in proliferative capacity and molecular signature: quiescent NSCs (qNSCs), primed NSCs (pNSCs), and activated NSCs (aNSCs). There is currently a void in terms of the specific markers available to effectively discern between these transient states. Likewise, the molecular signaling mechanisms controlling the transition from quiescence to activation remain largely unexplored, as do the factors influencing the decision between differentiation and self-renewal during NSC division. Here, we present evidence that the metabotropic P2Y13 purinergic receptor plays a critical role in regulating adult neurogenesis. We found that P2Y13 is specifically expressed in NSCs within the adult SEZ and that its levels can be used to distinguish qNSCs from aNSCs. Functionally, P2Y13 signaling promotes NSC activation, enhancing lineage progression, while dampening their self-renewal capacity. Conversely, pharmacological blockade or genetic silencing of the P2Y13 receptor favors NSC quiescence. Thus, we identified the metabotropic P2Y13 purinergic receptor as a pivotal modulator of NSC dynamics, influencing both the balance between NSC quiescence and activation and the mode of NSC division at the subependymal zone.

neuroscience↗

bioRxiv2023

CRISPR/Cas9 screenings unearth protein arginine methyltransferase 7 as a novel driver of metastasis in prostate cancer

Owing to the inefficacy of available treatments, the survival rate of patients with metastatic prostate cancer (mPCa) is severely decreased. Therefore, it is crucial to identify new therapeutic targets to increase their survival. This study aim was to identify the most relevant regulators of mPCa onset by performing two high-throughput CRISPR/Cas9 screenings. Furthermore, some of the top hits were validated using small interfering RNA (siRNA) technology, with protein arginine methyltransferase 7 (PRMT7) being the best candidate. Its inhibition or depletion via CRISPR significantly reduced mPCa cell capacities in vitro. Moreover, PRMT7 ablation reduced mPCa appearance in chicken chorioallantoic membrane and mouse xenograft assays. Molecularly, PRMT7 reprograms the expression of several adhesion molecules through methylation of several transcription factors, such as FoxK1 or NR1H2, which results in primary tumor PCa cell adhesion loss and motility gain. Importantly, PRMT7 is upregulated in advanced stages of Spanish PCa tumor samples and PRMT7 pharmacological inhibition reduces the dissemination of mPCa cells. Thus, here is shown that PRMT7 is a potential therapeutic target and biomarker of mPCa.

cancer biology↗