Sphingosine-1-phosphate signaling regulates the ability of Müller glia to become neurogenic, proliferating progenitor-like cells

The purpose of these studies is to investigate how Sphingosine-1-phosphate (S1P) signaling regulates glial phenotype, dedifferentiation of Müller glia (MG), reprogramming into proliferating MG-derived progenitor cells (MGPCs), and neuronal differentiation of the progeny of MGPCs in the chick retina. We found that S1P-related genes are highly expressed by retinal neurons and glia, and levels of expression were dynamically regulated following retinal damage. Drug treatments that activate S1P receptor 1 (S1PR1) or increase levels of S1P suppressed the formation of MGPCs. Conversely, treatments that inhibit S1PR1 or decrease levels of S1P stimulated the formation of MGPCs. Inhibition of S1P receptors or S1P synthesis significantly enhanced the neuronal differentiation of the progeny of MGPCs. We report that S1P-related gene expression in MG is modulated by microglia and inhibition of S1P receptors or S1P synthesis partially rescues the loss of MGPC formation in damaged retinas missing micro..., We analyzed scRNA-seq libraries that were generated and characterized previously (Campbell et al., 2021b; Campbell et al., 2022; El-Hodiri et al., 2022; El-Hodiri et al., 2023, 2021; Hoang et al., 2020; Li et al., 2023; Lyu et al., 2023). Dissociated cells were loaded onto the 10X Chromium Cell Controller with Chromium 3’ V2, V3 or Next GEM reagents. Using Seurat toolkits (Powers and Satija, 2015; Satija et al., 2015), Uniform Manifold Approximation and Projection (UMAP) for dimensional reduction plots were generated from 9 separate cDNA libraries, including 2 replicates of control undamaged retinas, and retinas at different times after NMDA-treatment. Seurat was used to construct gene lists for differentially expressed genes (DEGs), violin/scatter plots, and dot plots. Significance of difference in violin/scatter plots was determined using a Wilcoxon Rank Sum test with Bonferroni correction. Genes that were used to identify different types of retinal cells included the following: (1) M..., , # Sphingosine-1-phosphate signaling regulates the ability of Müller glia to become neurogenic, proliferating progenitor-like cells

[https://doi.org/10.5061/dryad.tdz08kq8t](https://doi.org/10.5061/dryad.tdz08kq8t)

## General Information

**Dataset Overview**

A detailed description of the general framework and specific methodology can be found in the relevant publication ([https://doi.org/10.7554/eLife.102151.4](https://doi.org/10.7554/eLife.102151.4)). 

For each dataset, barcode, feature, and matrix file from CellRanger output are provided.  These files serve as inputs for preparing the Seurat objects used in this study.  Barcode files contain a list of cell barcodes.  Feature files contain gene names from the reference used for CellRanger and include 3 columns: ENSEMBL number, gene name, and the type of assay run (\"GENE EXPRESSION\").  Matrix files contain the sparse matrix containing UMI counts for each library.

Dissociated cells were loaded onto the 10X Chromium Cell Controller ...,