Expression status transition of  NOTCH1 accompanies chromatin remodeling in human early retinal progenitor cells

Notch signaling, especially via the Notch1 receptor, is involved in normal eye development by maintaining retinal progenitor cell state before their differentiation, although the regulatory mechanism of fine-tuned Notch1 expression is unclear.

We re-analyzed publicly available human fetal retina single-cell RNA/ATAC-seq data at days 59, 74, and 78, using Seurat/Signac pipelines.

We observed NOTCH1 expression in retinal progenitor cells, which diminished at later stages of differentiation. Integration of single-cell RNA-seq and ATAC-seq revealed a decrease in chromatin accessibility at the NOTCH1 locus, accompanied by a decrease in its mRNA expression during differentiation into bipolar cells, horizontal cells, or retinal ganglion cells. Importantly, those chromatin remodeling regions contained the binding motifs of the RAX transcription factor, which is essential for retinal progenitor cells, Muller glia, and cones. This result suggested that the regulation of NOTCH1 expression might be achieved by chromatin remodeling at the NOTCH1 locus, although single-cell RNA-seq analysis suggested that RAX expression regulation might also contribute to NOTCH1 expression.

By analyzing retinal cell differentiation, this study identified a putative RAX binding site in the NOTCH1 locus and raised the possibility that NOTCH1 expression could be regulated by chromatin remodeling.