Biology subjects

Arts, J. A.

Publications and source records attributed to Arts, J. A..

3 recordsLinked to original sources

bioRxiv2025

Perturbation of epithelial and limbal stem cell identity in a mouse model of pathologic corneal neovascularization

The epithelial layer of the cornea is a critical physical and ocular immune barrier for maintaining tissue integrity, homeostasis, and transparency for proper vision. Corneal injury can trigger inflammation, impair wound healing and compromise immune privilege and avascularity, leading to vision loss. Moreover, injury to the cornea can disrupt the engine of epithelial repair and restoration, the limbal stem cell (LSC) niche. Here we used a corneal suture model to induce epithelial damage, sustained inflammation and neovascularization, to examine the impact on LSCs. Using single-cell transcriptomics, we analyzed corneal cell state changes and additionally evaluated the potential of duloxetine, an FDA-approved medicine, to promote wound healing and corneal homeostasis. Single-cell RNA-seq analysis revealed loss of homeostatic limbal stem cells, basal and differentiated epithelial cells and an increase in distinct limbal-like, conjunctival, inflammatory, and vascular cell states, suggesting a coordinated wound healing response in different tissue layers. Importantly, duloxetine treatment promoted epithelial homeostasis, enhanced stem cell-like and stromal repair processes, and suppressed immune and vascular responses. Examination of corneal cell perturbation and transformations at the single-cell level thorough marker profile annotations can improve the understanding of LSC plasticity and function while yielding potential biomarkers of corneal repair processes.

molecular biology↗

bioRxiv2024

Prediction of Cell States and Key Transcription Factors of the Human Cornea through Integrated Single-Cell Omics Analyses

The cornea, a transparent tissue composed of multiple layers, allows light to enter the eye. Several single-cell RNA-seq analyses have been performed to explore the cell states and to understand the cellular composition of the human cornea. However, the inconsistences in cell state annotations between these studies complicate the application of these findings in corneal studies. To address this, we integrated single-cell RNA-seq data from four published studies and created a human corneal cell state meta-atlas. This meta-atlas was subsequently evaluated in two applications. First, we developed a machine learning pipeline cPredictor, using the human corneal cell state meta-atlas as input, to annotate corneal cell states. We demonstrated the accuracy of cPredictor and its ability to identify novel marker genes and rare cell states in the human cornea. Furthermore, cPredictor revealed the differences of the cell states between pluripotent stem cell-derived corneal organoids and the human cornea. Second, we integrated the single-cell RNA-seq based cell state meta-atlas with chromatin accessibility data, conducting motif-focused and gene regulatory network analyses. These approaches identified distinct transcription factors driving cell states of the human cornea. The novel marker genes and transcription factors were validated by immunohistochemistry. Overall, this study offers a reliable and accessible reference for profiling corneal cell states, which facilitates future research in cornea development, disease and regeneration. Significance statementThis study creates a human corneal cell state meta-atlas that provides a common nomenclature of cells in the human cornea, through integrating multiple single-cell RNA-seq analyses. Using this meta-atlas, we developed a machine learning pipeline, cPredictor, to accurately annotate cell states in corneal studies using single-cell RNA-seq. Additionally, we identified distinct transcription factors driving cell states through integrating the atlas with chromatin accessibility data. This meta-atlas and the computational tool cPredictor enable future research in cornea development, disease, and regeneration.

cell biology↗

bioRxiv2022

Gut microbiota of homing pigeons shows summer-winter variation under constant diet indicating a substantial effect of temperature

BackgroundGut microbiotas play a pivotal role in host physiology and behaviour, and may affect host life-history traits such as seasonal variation in host phenotypic state. Generally, seasonal gut microbiota variation is attributed to seasonal diet variation. However, seasonal temperature and day length variation may also drive gut microbiota variation. We investigated summer-winter differences in gut microbiota in 14 homing pigeons living outdoors under a constant diet by collecting cloacal swabs in both seasons during two years. Because temperature effects may be mediated by host metabolism, we determined basal metabolic rate (BMR) and body mass. Immune competence is influenced by day length and has a close relationship with gut microbiota, and it may thus be a link between day length and gut microbiota. Therefore, we measured seven innate immune indices. We expected gut microbiota to show summer-winter differences and gut microbiota to correlate with metabolism and immune indices. ResultsBMR, body mass, and two immune indices varied seasonally, other host factors did not. Gut microbiota showed differences between seasons and sexes, and correlated with metabolism and immune indices. The most abundant genus (Lachnoclostridium 12, 12%) and associated higher taxa, were more abundant in winter, though not significantly at the phylum level, Firmicutes. Bacteroidetes were more abundant in summer. The Firmicutes:Bacteroidetes ratio tended to be higher in winter. The KEGG ortholog functions for fatty acid biosynthesis and linoleic acid metabolism (PICRUSt2) had increased abundances in winter. ConclusionsThe gut microbiota of homing pigeons varied seasonally, even under a constant diet. The correlations between immune indices and gut microbiota did not involve consistently specific immune indices and included only one of the two immune indices that showed seasonal differences, suggesting that immune competence may be an unlikely link between day length and gut microbiota. The correlations between gut microbiota and metabolism indices, the higher Firmicutes:Bacteroidetes ratio in winter, and the resemblance of the summer-winter differences in gut microbiota with the general temperature effects on gut microbiota in the literature, suggest that temperature partly drove the summer-winter differences in gut microbiota in homing pigeons.

microbiology↗