Abstract
Multiple transcription factors containing the bHLH motif are expressed during retinogenesis. Their precise functions and interactions in uncommitted retinal progenitors remain to be fully elucidated. Here, we investigate the roles of bHLH factors in human ES cell-derived 3D retinal organoids by elevating ATOH7 and Neurog2 expression. Single cell transcriptome analyses identify three progenitor states in retinal organoids: neural stem cell-like, neurogenic, and cell cycle-exiting progenitors, which feed into a postmitotic neuroblast pool that gives rise to early born neuronal lineages. Both ATOH7 and Neurog2 accelerate the transition from the stem cell to the neurogenic state, expand the exiting progenitor and neuroblast populations, and significantly enhance retinal ganglion cell production. However, ATOH7 and Neurog2 differentially promote neuronal types with distinct molecular characteristics. Moreover, single cell transcriptome analyses reveal novel insight that ATOH7 and Neurog2 modulate an intricate interactive gene network, thus impacting the competence states and fate choices of uncommitted progenitors.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
The revision has reduced the word count for the abstract to 150. The revision has combined supplementary data with the main manuscript. The revision has changed the author order.