Expression profiling of Aldh1l1-precursors in the developing spinal cord reveals glial lineage-specific genes and direct Sox9-Nfe2l1 interactions. Mus musculus

Developmental regulation of gliogenesis in the mammalian CNS is incompletely understood, in part due to a limited repertoire of lineage-specific genes. We used Aldh1l1-GFP as a marker for gliogenic radial glia and later-stage precursors of developing astrocytes and performed gene expression profiling of these cells. We then used this dataset to identify candidate transcription factors that may serve as glial markers or regulators of glial fate. Our analysis generated a database of developmental stage-related markers of Aldh1l1+ cells between murine embryonic day 13.5-18.5. Using these data we identify the bZIP transcription factor Nfe2l1 and demonstrate that it promotes glial fate under direct Sox9 regulatory control. Thus, this dataset represents a resource for identifying novel regulators of glial development. Overall design: 18 total samples consisting of three biological replicates each of flow sorted embryonic spinal cord Aldh1l1-GFP positive cells and whole cord, spanning the radial glial to astrocyte transition

哺乳动物中枢神经系统（CNS）胶质发生的发育调控机制尚未完全阐明，其部分原因在于谱系特异性基因的可用储备较为有限。本研究以Aldh1l1-GFP作为胶质生成型放射状胶质细胞及发育中星形胶质细胞晚期前体的标记物，对上述细胞开展了基因表达谱分析。随后，本研究利用该数据集筛选出可作为胶质细胞标记物或胶质命运调控因子的候选转录因子。我们的分析构建了小鼠胚胎第13.5天至18.5天之间Aldh1l1阳性（Aldh1l1+）细胞的发育阶段相关标记物数据库。借助上述数据，我们鉴定出碱性亮氨酸拉链（bZIP）家族转录因子Nfe2l1，并证实其在Sox9的直接调控下促进胶质细胞命运决定。因此，本数据集可作为筛选胶质发育新型调控因子的研究资源。
实验设计：共包含18个样本，分别为经流式分选的胚胎脊髓Aldh1l1-GFP阳性细胞与完整脊髓组织，每组各设3次生物学重复，实验覆盖了从放射状胶质细胞到星形胶质细胞的转变过程。