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Studies were incorporated in a barcode, matrix, feature format. This format can be found on the
10x Genomics website
for processing of single cell studies to obtain the gene expression matrices.
For each study, the metadata incorporated in GEO were manually curated into profiles and the samples were separated based on applicable groups and conditions.
The expression data from the cells for the samples within the same profile and condition were aggregated into an expression matrix with the cell barcodes having the sample name appended to it to ensure unique cell names.
Description (from GEO)
Submission Date: Mar 31, 2021
Summary: Objective: beta-cell dedifferentiation has been revealed as a pathological mechanism underlying pancreatic dysfunction in diabetes. However, exactly how such dedifferentiation process affects beta-cell gene expression and islet microenvironment remains incompletely understood Method: We performed single-cell RNA-Sequencing (RNA-seq) in islets obtained from beta-cell-specific miR-7a2 overexpressing mice (Tg7), a murine model of beta-cell dedifferentiation and diabetes. Results: Single-cell RNA-seq revealed that beta-cell dedifferentiation is associated with the induction of genes associated with epithelial to mesenchymal transition (EMT) specifically in beta-cells of diabetic (12-week-old) Tg7 mice. These molecular changes are associated with a weakening of beta-cell:beta-cell contacts, increased extracellular matrix (ECM) deposition and TGFb-dependent islet fibrosis. We find that the mesenchymal reprogramming of beta-cells is explained in part by the downregulation of Pdx1 and its inability to regulate a myriad of target genes preserving the epithelial cell phenotype. Notable among epithelial genes transactivated by Pdx1 is Ovol2, a transcriptional repressor of the EMT transcription factor ZEB2. Following compromised beta-cell identity, the reduction of Pdx1 mRNA levels decreases Ovol2 gene expression, which triggers mesenchymal reprogramming of beta-cells through the induction of Zeb2. Finally, we provided evidence that EMT signalling associated with the upregulation of Zeb2 expression is a molecular feature of islet of T2D subjects. Conclusions: Our study indicates that beta-cell dedifferentiation triggers a chronic response to tissue injury, which alters the pancreatic islet microenvironment and contribute to islet fibrosis. It suggests that regulators of EMT signalling may represent novel therapeutic targets for the treatment of beta-cell dysfunction and fibrosis in T2D.
GEO Accession ID: GSE171252
PMID: 33989778
Preprocessing and downstream analysis were computed using the scanpy Python library and the
steps of processing followed the Seurat vignette. Cells and genes with no expression or very low expression were
removed from the dataset based on a predefined threshold. The data was then normalized across the expression within the cells and log normalized. The top 2000 highly variable genes were extracted to be used for downstream analysis.
For each of these aggregated data matrices, the clusters were computed using the leiden algorithm. Scanpy was then used to compute the PCA, t-SNE, and UMAPs.
The points in the plots are labelled by their corresponding cell type labels. The cell type labels were computed using the wilcoxon method as the differential gene expression method.
The top 250 genes were then used for enrichment analysis against the CellMarker library in order to determine the most appropriate cell type label with the lowest p-value.
Select conditions below to toggle them from the plot:
| Cell Types | Cell Samples |
|---|---|
Differential gene expression can be computed for a single cell type labeled group of cells vs the rest.
These include wilcoxon,
DESeq2, or characteristic direction.