Dynamics of transcription regulatory network during mice-derived retina organoid development

The retina is a complex system containing several neuron types arranged in distinct layers. Many aspects of the retina's development and the molecular events in the human light-sensing system have been previously unveiled. However, there is limited information about regulatory networks governing the transitional stages during retina development. To address this issue, we have studied the transcriptome dynamics of mice-derived retinal organoid development in 10 successive time-points, from stem cell to functional retina. For the first time, we have identified the main modules of genes related to different stages of development and predicted all possible transcription factors. A major shift in the transcriptome occurs during the transition of cells from D0 to D10 and again at the late stages of retina development. Transcription, nervous system development, cell cycle, neurotransmitter transport, glycosylation, and lipid metabolisms are the most important biological processes during retina development. Altogether, we have identified and reported 15 TFs, including Irx2, Irx3, Lmo2, Tead2, Tbx20, and Zeb1, which are potentially involved in the regulation of retinal organoid development. In conclusion, using several rigorous analyses, we have found main stage-specific biological processes in the retina development and predicted TFs with strong potency in controlling this structure.