Biology subjects

Cantu, A.

Publications and source records attributed to Cantu, A..

5 recordsLinked to original sources

bioRxiv2026

Allelic variation at a terpene synthase locus shapes wine monoterpene composition and aroma

The genetic basis of wine monoterpene variation and its sensory consequences remain poorly understood. We investigated how allelic variation at a chromosome 10 linalool QTL harboring a terpene synthase cluster, including VviTPS54, influences wine aroma in a Riesling x Cabernet Sauvignon mapping population. Twenty-six wines from progeny selected for contrasting genotypes were subjected to HS-SPME-GC-MS profiling and descriptive sensory analysis. Genotypes carrying the high-linalool Riesling allele produced substantially elevated monoterpene levels dominated by (3S)-linalool. Berry and wine monoterpene profiles were significantly correlated, and berry monoterpene glycosides showed broad correlations with wine monoterpenes. High-monoterpene genotypes were more closely associated with Floral, Tropical Fruit, and Apricot/Peach attributes, though perception was modulated by matrix effects from berry pigmentation. These results demonstrate that allelic variation at a terpene synthase locus drives coordinated changes in wine monoterpene composition and linked sensory attributes, while underscoring the complexity of translating genetic variation into sensory outcomes.

genetics↗

bioRxiv2025

Patient-derived airway organoids from BAL fluid model injury and therapy responses in neonatal bronchopulmonary dysplasia

Lung tissue from fetal and neonatal lung samples is tough to obtain, and capturing cells from a living patient with evolving or established disease is very challenging. We hypothesized that airway organoids derived from bronchoalveolar lavage (BAL) samples obtained from intubated preterm infants with bronchopulmonary dysplasia (BPD) will recapitulate the epithelial heterogeneity seen in human airways and can be used to study lung injury and therapeutic response in vitro. Here, we demonstrate that BAL sample-derived airway organoids from ventilator-dependent patients with established BPD exhibited cellular heterogeneity consistent with that observed in the human airway. Developed organoids contain basal cell progenitors and a spectrum of differentiated epithelial subtypes, including secretory, ciliated, PNECs, and hillock cells. Hyperoxia exposure and treatment with dexamethasone caused significant cellular transcriptional changes and highlighted biological pathways, both known and novel, with distinct findings based on sex as a biological variable. Findings were validated in an independent dataset from human BPD lung samples. Infant BAL-derived human lung organoids represent a cutting-edge model that bridges a critical gap in BPD research. They combine the advantages of being patient-specific and capturing developmental lung biology, with the experimental flexibility of an in vitro system.

developmental biology↗

bioRxiv2023

Modulation of Recovery from Neonatal Hyperoxic Lung Injury by Sex as a Biological Variable

Recovery from lung injury during the neonatal period requires the orchestration of many biological pathways. The modulation of such pathways can drive the developing lung towards proper repair or persistent maldevelopment that can lead to a disease phenotype. Sex as a biological variable can regulate these pathways differently in the male and female lung exposed to neonatal hyperoxia. In this study, we assessed the contribution of cellular diversity in the male and female neonatal lung following injury. Our objective was to investigate sex and cell-type specific transcriptional changes that drive repair or persistent injury in the neonatal lung and delineate the alterations in the immune-endothelial cell communication networks using single cell RNA sequencing (sc-RNAseq) in a murine model of hyperoxic injury. We generated transcriptional profiles of >55,000 cells isolated from the lungs of postnatal day 1 (PND 1) and postnatal day 21 (PND 21) neonatal male and female C57BL/6 mice exposed to 95% FiO2 between PND 1-5 (saccular stage of lung development). We show the presence of sex-based differences in the transcriptional states of lung endothelial and immune cells at PND 1 and PND 21. Furthermore, we demonstrate that biological sex significantly influences the response to injury, with a greater number of differentially expressed genes showing sex-specific patterns than those shared between male and female lungs. Pseudotime trajectory analysis highlighted genes needed for lung development that were altered by hyperoxia. Finally, we show intercellular communication between endothelial and immune cells at saccular and alveolar stages of lung development with sex-based biases in the crosstalk and identify novel ligand-receptor pairs. Our findings provide valuable insights into the cell diversity, transcriptional state, developmental trajectory, and cell-cell communication underlying neonatal lung injury, with implications for understanding lung development and possible therapeutic interventions while highlighting the crucial role of sex as a biological variable.

developmental biology↗

bioRxiv2022

Remarkable Sex-Specific Differences at Single-Cell Resolution in Neonatal Hyperoxic Lung Injury

Exposure to supraphysiological concentrations of oxygen (hyperoxia) predisposes to bronchopulmonary dysplasia (BPD), which is characterized by abnormal alveolarization and pulmonary vascular development, in preterm neonates. Neonatal hyperoxia exposure is used to recapitulate the phenotype of human BPD in murine models. Male sex is considered an independent predictor for the development of BPD, but the main mechanisms underlying sexually dimorphic outcomes are unknown. Our objective was to investigate sex-specific and cell-type specific transcriptional changes that drive injury in the neonatal lung exposed to hyperoxia at single-cell resolution and delineate the changes in cell-cell communication networks in the developing lung. We used single cell RNA sequencing (scRNAseq) to generate transcriptional profiles of >35000 cells isolated from the lungs of neonatal male and female C57BL/6 mice exposed to 95% FiO2 between PND1-5 (saccular stage of lung development) or normoxia and euthanized at PND7 (alveolar stage of lung development). ScRNAseq identified 22 cell clusters with distinct populations of endothelial, epithelial, mesenchymal, and immune cells. Our data identified that the distal lung vascular endothelium (composed of aerocytes and general capillary endothelial cells) is exquisitely sensitive to hyperoxia exposure with the emergence of an intermediate capillary endothelial population with both aCaP and gCaP markers. We also identified a myeloid derived suppressor cell population from the lung neutrophils. Sexual dimorphism was evident in all lung cell subpopulations but was striking among the lung immune cells. Finally, we identified that the specific intercellular communication networks and the ligand-receptor pairs that are impacted by neonatal hyperoxia exposure.

developmental biology↗

bioRxiv2019

Global phylogeography and ancient evolution of the widespread human gut virus crAssphage

Microbiomes are vast communities of microbes and viruses that populate all natural ecosystems. Viruses have been considered the most variable component of microbiomes, as supported by virome surveys and examples of high genomic mosaicism. However, recent evidence suggests that the human gut virome is remarkably stable compared to other environments. Here we investigate the origin, evolution, and epidemiology of crAssphage, a widespread human gut virus. Through a global collaboratory, we obtained DNA sequences of crAssphage from over one-third of the worlds countries, and showed that its phylogeography is locally clustered within countries, cities, and individuals. We also found colinear crAssphage-like genomes in both Old-World and New-World primates, challenging genomic mosaicism and suggesting that the association of crAssphage with primates may be millions of years old. We conclude that crAssphage is a benign globetrotter virus that may have co-evolved with the human lineage and an integral part of the normal human gut virome.

microbiology↗