Department of Ophthalmology/Ross Eye Institute, University at Buffalo, Buffalo, NY, USA.
New York State Center of Excellence in Bioinformatics and Life Sciences, University at Buffalo, Buffalo, NY, USA.
Nat Commun. 2021 Mar 5;12(1):1465. doi: 10.1038/s41467-021-21704-4.
Atoh7 has been believed to be essential for establishing the retinal ganglion cell (RGC) lineage, and Pou4f2 and Isl1 are known to regulate RGC specification and differentiation. Here we report our further study of the roles of these transcription factors. Using bulk RNA-seq, we identify genes regulated by the three transcription factors, which expand our understanding of the scope of downstream events. Using scRNA-seq on wild-type and mutant retinal cells, we reveal a transitional cell state of retinal progenitor cells (RPCs) co-marked by Atoh7 and other genes for different lineages and shared by all early retinal lineages. We further discover the unexpected emergence of the RGC lineage in the absence of Atoh7. We conclude that competence of RPCs for different retinal fates is defined by lineage-specific genes co-expressed in the transitional state and that Atoh7 defines the RGC competence and collaborates with other factors to shepherd transitional RPCs to the RGC lineage.
Atoh7 被认为对于建立视网膜神经节细胞（RGC）谱系至关重要，而 Pou4f2 和 Isl1 则已知调节 RGC 的特化和分化。在这里，我们报告了对这些转录因子作用的进一步研究。使用批量 RNA-seq，我们确定了受这三个转录因子调控的基因，这扩展了我们对下游事件范围的理解。使用 scRNA-seq 在野生型和突变型视网膜细胞上，我们揭示了视网膜祖细胞（RPC）的一个过渡细胞状态，该状态由 Atoh7 和其他不同谱系的基因标记，并由所有早期视网膜谱系共享。我们进一步发现，在没有 Atoh7 的情况下，RGC 谱系的出现出乎意料。我们得出结论，不同视网膜命运的 RPC 能力由过渡状态中共同表达的谱系特异性基因定义，Atoh7 定义了 RGC 的能力，并与其他因子合作，将过渡性 RPC 推向 RGC 谱系。
