Biology subjects

Nguyen, T. T. V.

Publications and source records attributed to Nguyen, T. T. V..

4 recordsLinked to original sources

bioRxiv2026

NGFR/Ngfr-marked basal duct progenitors drive ductal--acinar regeneration in injured salivary glands

Severe salivary gland injury can cause chronic xerostomia and persistent secretory dysfunction, yet the epithelial populations that support repair remain poorly defined. Here, we identify NGFR/Ngfr as a conserved surface marker for isolating organoid-forming epithelial stem/progenitor cells from human and mouse salivary glands and show that mouse Ngfr-lineage cells contribute to ductal-acinar regeneration after injury. Single-cell transcriptomic analysis of human salivary gland tissue identified a restricted NGFR-expressing basal duct epithelial subpopulation with progenitor-like features and early positions along inferred epithelial differentiation trajectories. Functionally, NGFR-expressing cells showed enhanced primary and secondary organoid-forming capacity, and NGFR-enriched human organoids engrafted after transplantation into injured salivary glands of immunodeficient mice. In mouse salivary glands, isolated Ngfr-expressing cells showed enriched organoid-forming activity, and Ngfr expression localized to injury-associated ductal regions after duct ligation and local inflammatory injury. Ngfr-CreERT2 lineage tracing further showed that Ngfr-lineage cells contribute to ductal and acinar compartments during post-injury regeneration. Together, these findings establish NGFR/Ngfr as a conserved surface marker for prospectively isolating basal duct epithelial stem/progenitor populations with organoid-forming activity and injury-responsive ductal-acinar regenerative potential.

cell biology↗

bioRxiv2026

Impact of temperature on patient-derived dengue virus breakthrough infections in wMel-infected Aedes aegypti.

The wMel strain of the insect endosymbiont Wolbachia reduces the potential for Aedes aegypti to transmit mosquito-borne viruses such as dengue (DENV). Field trials that have introgressed wMel into Ae. aegypti populations have shown this approach significantly reduces dengue incidence. In a laboratory setting some wMel-Ae. aegypti develop infectious saliva following a viremic blood meal. Additionally, studies have demonstrated that exposing wMel-Ae. aegypti to heat treatment, particularly during the larval stage, reduces wMel density in key tissues such as the ovaries, midgut and salivary glands. Here we build on these studies, using viremic blood collected from 13 dengue inpatients at the Hospital for Tropical Diseases in Ho Chi Minh City (Viet Nam), to assess how temperature affects the protection afforded to Ae. aegypti by wMel. We found that, compared to wMel-Ae. aegypti reared at 28 {+/-} 4{degrees}C, those reared at 31 {+/-} 4{degrees}C developed infectious saliva more frequently, but the risk of this occurring was still reduced compared to WT mosquitoes reared at the same temperature. Heat treatment reduced the density of wMel in all tissues tested, decreased the magnitude of wMels protection against DENV replication in the head/thorax, and significantly increased the amount of DENV replication in wMel-Ae. aegypti. When comparing cohorts of wMel-Ae. aegypti that did or did not develop infectious saliva, DENV levels in the head/thorax were associated with increased odds of mosquitoes developing infectious saliva, but wMel density was not. Overall, these findings show that elevated rearing temperatures increase the risk of patient-derived DENV breakthrough infections in wMel-Ae. aegypti, potentially due to increased DENV replication in these mosquitoes. This limitation suggests it would be prudent to increase surveillance in regions using wMel for dengue control when daily mean temperatures remain above 30{degrees}C for multiday periods. Author SummaryThe mosquito species Ae. aegypti can be infected with the bacterium Wolbachia (wMel strain), reducing its capacity to transmit viruses like dengue (DENV). Wolbachia is now being used as a biocontrol tool to reduce the burden of dengue in communities. However, some mosquitoes with Wolbachia can still transmit DENV. Here we utilised a natural infection model using dengue patient-derived blood to examine how temperature may increase the risk of DENV transmission occurrence in mosquitoes with wMel. Mosquitoes with wMel were more likely to transmit virus when reared at an average temperature of 31{degrees}C compared to those reared at an average temperature of 28{degrees}C but these mosquitoes still had a lower risk of developing infectious saliva compared to their wMel-free counterparts. Higher temperatures reduced the amount of wMel in mosquito tissues and increased the amount of DENV replicating in the head/thorax. Increasing levels of DENV RNA in these tissues were found to be associated with increased risk of mosquitoes with wMel developing infectious saliva. This finding indicates surveillance is warranted in high temperature settings or during heat waves, to monitor for changes in wMel frequency and DENV infection in Ae. aegypti.

microbiology↗

bioRxiv2023

The T Cell Receptor beta Chain Repertoire of Tumor Infiltrating Lymphocytes Improves Neoantigen Prediction and Prioritization

In the realm of cancer immunotherapy, the meticulous selection of neoantigens plays a fundamental role in enhancing personalized treatments. Traditionally, this selection process has heavily relied on predicting the binding of peptides to human leukocyte antigens (pHLA). Nevertheless, this approach often overlooks the dynamic interaction between tumor cells and the immune system. In response to this limitation, we have developed an innovative prediction algorithm rooted in machine learning, integrating T cell receptor {beta} chain (TCR{beta}) profiling data from colorectal cancer (CRC) patients for a more precise neoantigen prioritization. TCR{beta} sequencing was conducted to profile the TCR repertoire of tumor-infiltrating lymphocytes (TILs) from 28 CRC patients. The data unveiled both intra-tumor and inter-patient heterogeneity in the TCR{beta} repertoires of CRC patients, likely resulting from the stochastic utilization of V and J segments in response to neoantigens. Our novel combined model integrates pHLA binding information with pHLA-TCR binding to prioritize neoantigens, resulting in heightened specificity and sensitivity compared to models using individual features alone. The efficacy of our proposed model was corroborated through ELISpot assays on long peptides, performed on four CRC patients. These assays demonstrated that neoantigen candidates prioritized by our combined model outperformed predictions made by the established tool NetMHCpan. This comprehensive assessment underscores the significance of integrating pHLA binding with pHLA-TCR binding analysis for more effective immunotherapeutic strategies.

cancer biology↗

bioRxiv2023

Improvement in Neoantigen Prediction via Integration of RNA Sequencing Data for Variant Calling

Neoantigen-based immunotherapy has emerged as a promising strategy for improving the life expectancy of cancer patients. This therapeutic approach heavily relies on accurate identification of cancer mutations using DNA sequencing (DNAseq) data. However, current workflows tend to provide a large number of neoantigen candidates, of which only a limited number elicit efficient and immunogenic T-cell responses suitable for downstream clinical evaluation. To overcome this limitation and increase the number of high-quality immunogenic neoantigens, we propose integrating RNA sequencing (RNAseq) data into the mutation identification step in the neoantigen prediction workflow. In this study, we characterize the mutation profiles identified from DNAseq and/or RNAseq data in tumor tissues of 25 patients with colorectal cancer (CRC). We detected only 22.4% of variants shared between the two methods. In contrast, RNAseq-derived variants displayed unique features of affinity and immunogenicity. We further established that neoantigen candidates identified by RNAseq data significantly increased the number of highly immunogenic neoantigens (confirmed by ELISpot) that would otherwise be overlooked if relying solely on DNAseq data. In conclusion, this integrative approach holds great potential for improving the selection of neoantigens for personalized cancer immunotherapy, ultimately leading to enhanced treatment outcomes and improved survival rates for cancer patients.

immunology↗