The SWI/SNF complexes are required for the differentiation and for inhibition of neural progenitor genes in the retinal pigmented epithelium

During embryonic development, tissue-specific transcription factors and chromatin remodelers function together to ensure gradual, coordinated differentiation of multiple lineages. Here, we define this regulatory interplay in the developing retinal pigmented epithelium (RPE), a neuroectodermal lineage essential for the development, function, and maintenance of the adjacent retina. We present a high-resolution spatial transcriptomic atlas of the developing RPE and the adjacent ocular mesenchyme, obtained by geographic positional sequencing (Geo-Seq) of a single development stage of the eye, encompassing young and more mature ocular progenitors. These transcriptomic data, available through an online web tool, reveal the major transcription factors and their gene regulatory networks that control over 5000 genes during RPE and ocular mesenchyme differentiation. We also present evidence, based on conditional inactivation followed by Geo-seq, that this differentiation program is dependent on the activity of the SWI/SNF complexes. We find that these complexes are required for the expression and activity of the RPE TFs and inhibition of the competing neuronal progenitor and cell proliferation genes. The persistent expression of proliferation genes, despite the onset of neurogenesis upon SWI/SNF elimination, supports the tumor suppressive activity of these complexes. Our work reveals that the TFs regulation of a timely, gradual differentiation program, as well as maintenance of cell fate and ensuring exit from the cell cycle, depends on the chromatin terrine defined by the SWI/SNF chromatin remodelers.