UNASSIGNED: Single-cell RNA sequencing (scRNA-seq) data on the retinas from 35 retina samples of 3 species (human, mouse, and zebrafish) including 259,087 cells were adopted to perform a comparative analysis across species. Bioinformatic tools were used to conduct weighted gene co-expression network analysis (WGCNA), single-cell regulatory network analysis, cell-cell communication analysis, and trajectory inference analysis.
UNASSIGNED: The cross-species comparison revealed shared or species-specific gene expression patterns at single-cell resolution, such as the stathmin family genes, which were highly expressed specifically in zebrafish Müller glias (MGs). Thirteen gene modules were identified, of which nine were associated with retinal cell types, and Gene Ontology (GO) enrichment of module genes was consistent with cell-specific highly expressed genes. Many IRD genes were identified as hub genes and cell-specific regulons. Most IRDs, especially the retinitis pigmentosa (RP) genes, were enriched in rod-specific regulons. Integrated expression and transcription regulatory network genes, such as congenital stationary night blindness (CSNB) genes GRK1, PDE6B, and TRPM1, showed cell-specific expression and transcription characteristics in either rods or bipolar cells (BCs). IRD genes showed evolutionary conservation (GNAT2, PDE6G, and SAG) and divergence (GNAT2, MT-ND4, and PDE6A) along the trajectory of photoreceptors (PRs) among species. In particular, the Leber congenital amaurosis (LCA) gene OTX2 showed high expression at the beginning of the trajectory of both PRs and BCs.
UNASSIGNED: We identified molecular pathways and cell types closely connected with IRDs, bridging the gap between gene expression, genetics, and pathogenesis. The IRD genes enriched in cell-specific modules and regulons suggest that these diseases share common etiological bases. Overall, mining of interspecies transcriptome data reveals conserved transcriptomic features of retinas across species and promising applications in both normal retina anatomy and retina pathology.
■来自3种(人类,鼠标,和斑马鱼),包括259,087个细胞被用来进行跨物种的比较分析。生物信息学工具用于进行加权基因共表达网络分析(WGCNA),单细胞调控网络分析,细胞间通讯分析,和轨迹推断分析。
■跨物种比较揭示了单细胞分辨率下共有或物种特异性基因表达模式,比如Stathmin家族基因,在斑马鱼Müllerglias(MGs)中高度表达。确定了13个基因模块,其中9种与视网膜细胞类型有关,模块基因的基因本体论(GO)富集与细胞特异性高表达基因一致。许多IRD基因被鉴定为hub基因和细胞特异性调节子。大多数IRDs,尤其是视网膜色素变性(RP)基因,富含杆特异性调节子。整合表达和转录调控网络基因,如先天性固定夜盲症(CSNB)基因GRK1,PDE6B,和TRPM1在杆状或双极细胞(BC)中显示出细胞特异性表达和转录特征。IRD基因表现出进化保守性(GNAT2,PDE6G,和SAG)和沿物种之间光感受器(PR)轨迹的发散(GNAT2,MT-ND4和PDE6A)。特别是,Leber先天性黑蒙(LCA)基因OTX2在PR和BCs的运动轨迹开始时显示出高表达。
■我们确定了与IRD密切相关的分子途径和细胞类型,弥合基因表达之间的差距,遗传学,和发病机制。富含细胞特异性模块和调节子的IRD基因表明这些疾病具有共同的病因基础。总的来说,种间转录组数据的挖掘揭示了跨物种视网膜的保守转录组特征,并在正常视网膜解剖和视网膜病理学中具有良好的应用前景。