Single nuclei transcriptomics of the in situ human limbal stem cell niche

Davidson, Kathryn C.; Sung, Minkyung; Brown, Karl D.; Contet, Julian; Belluschi, Serena; Hamel, Regan; Moreno-Moral, Aida; dos Santos, Rodrigo L.; Gough, Julian; Polo, Jose M.; Daniell, Mark; Parfitt, Geraint J.

doi:10.1038/s41598-024-57242-4

Cited by 2 publications

References 33 publications

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

Arts,

Fallo,

Florencio

et al. 2024

Preprint

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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.

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

Arts,

Fallo,

Florencio

et al. 2024

Preprint

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Regulation of corneal epithelial differentiation: miR-141-3p promotes the arrest of cell proliferation and enhances the expression of terminal phenotype

Ortiz-Melo,

Campos,

Sánchez-Guzmán

et al. 2024

PLoS ONE

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In recent years, different laboratories have provided evidence on the role of miRNAs in regulation of corneal epithelial metabolism, permeability and wound healing, as well as their alteration after surgery and in some ocular pathologies. We searched the available databases reporting miRNA expression in the human eye, looking for miRNAs highly expressed in central cornea, which could be crucial for maintenance of the epithelial phenotype. Using the rabbit RCE1(5T5) cell line as a model of corneal epithelial differentiation, we describe the participation of miR-141-3p as a possible negative regulator of the proliferative/migratory phenotype in corneal epithelial cells. The expression of miR-141-3p followed a time course similar to the differentiation-linked KRT3 cytokeratin, being delayed 24–48 hours relative to PAX6 expression; such result suggested that miR-141-3p only regulates the expression of terminal phenotype. Inhibition of miR-141-3p led to increased cell proliferation and motility, and induced the expression of molecular makers characteristic of an Epithelial Mesenchymal Transition (EMT). Comparison between the transcriptional profile of cells in which miR-141-3p was knocked down, and the transcriptomes from proliferative non-differentiated and differentiated stratified epithelia suggest that miR-141-3p is involved in the expression of terminal differentiation mediating the arrest of cell proliferation and inhibiting the EMT in highly motile early differentiating cells.

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Single nuclei transcriptomics of the in situ human limbal stem cell niche

Cited by 2 publications

References 33 publications

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

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

Regulation of corneal epithelial differentiation: miR-141-3p promotes the arrest of cell proliferation and enhances the expression of terminal phenotype

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