Jarid2 promotes temporal progression of retinal progenitors via repression of Foxp1 [Foxp1 cKO bulk RNA-seq]

Transitions in competence underlie the ability of CNS progenitors to generate a diversity of neurons and glia. Retinal progenitor cells in mouse generate early-born cell types embryonically and late-born cell types largely postnatally. We find that the transition from early to late progenitor competence is regulated by Jarid2. Loss of Jarid2 results in extended production of early cell types and extended expression of early progenitor genes. Jarid2 can regulate histone modifications, and we find reduction of repressive mark H3K27me3 on a subset of early progenitor genes with loss of Jarid2, most notably Foxp1. We show that Foxp1 regulates the competence to generate early-born retinal cell types, promotes early and represses late progenitor gene expression, and is required for extending early retinal cell production after loss of Jarid2. We conclude Jarid2 facilitates progression of retinal progenitor temporal identity by repressing Foxp1, which is a primary regulator of early temporal patterning. Gene expression comparison, by bulk RNA-sequencing, of triplicate Foxp1 cKO and control littermates during early retinal development (e16.5).中枢神经系统（Central Nervous System, CNS）祖细胞的能力时序转变，是其生成多样化神经元与神经胶质细胞的核心基础。小鼠视网膜祖细胞在胚胎期生成早期诞生的细胞类型，而晚期诞生的细胞类型则主要在出生后产生。本研究发现，Jarid2可调控祖细胞从早期状态向晚期状态的能力转变。Jarid2缺失会导致早期细胞类型的生成过程延长，同时使早期祖细胞基因的表达持续上调。Jarid2能够调控组蛋白修饰，我们的研究显示，在Jarid2缺失时，部分早期祖细胞基因（尤以Foxp1为代表）的抑制性组蛋白标记H3K27me3水平显著降低。我们证实，Foxp1可调控视网膜早期诞生细胞类型的生成能力，促进早期祖细胞基因表达并抑制晚期祖细胞基因表达，同时在Jarid2缺失后延长早期视网膜细胞生成的过程中发挥必需作用。综上，Foxp1是早期视网膜时序模式的核心调控因子，Jarid2通过抑制Foxp1的表达，推动视网膜祖细胞的时序身份转变进程。本数据集为小鼠视网膜早期发育阶段（胚胎16.5天，e16.5）中，三组生物学重复的Foxp1条件性敲除（conditional knockout, cKO）小鼠与同窝对照小鼠的bulk RNA测序（bulk RNA-sequencing）基因表达对比数据。