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RNA splicing programs define tissue compartments and cell types at single cell resolution
eLife ( IF 6.4 ) Pub Date : 2021-09-13 , DOI: 10.7554/elife.70692
Julia Eve Olivieri 1, 2, 3 , Roozbeh Dehghannasiri 2, 3 , Peter L Wang 3 , SoRi Jang 3 , Antoine de Morree 4 , Serena Y Tan 5 , Jingsi Ming 6, 7 , Angela Ruohao Wu 8 , , Stephen R Quake 9, 10 , Mark A Krasnow 3 , Julia Salzman 2, 3
Affiliation  

The extent splicing is regulated at single-cell resolution has remained controversial due to both available data and methods to interpret it. We apply the SpliZ, a new statistical approach, to detect cell-type-specific splicing in >110K cells from 12 human tissues. Using 10x data for discovery, 9.1% of genes with computable SpliZ scores are cell-type-specifically spliced, including ubiquitously expressed genes MYL6 and RPS24. These results are validated with RNA FISH, single-cell PCR, and Smart-seq2. SpliZ analysis reveals 170 genes with regulated splicing during human spermatogenesis, including examples conserved in mouse and mouse lemur. The SpliZ allows model-based identification of subpopulations indistinguishable based on gene expression, illustrated by subpopulation-specific splicing of classical monocytes involving an ultraconserved exon in SAT1. Together, this analysis of differential splicing across multiple organs establishes that splicing is regulated cell-type-specifically.

中文翻译:


RNA 剪接程序以单细胞分辨率定义组织区室和细胞类型



由于可用的数据和解释它的方法,单细胞分辨率下剪接的调节程度仍然存在争议。我们应用 SpliZ(一种新的统计方法)来检测来自 12 种人体组织的 >110K 细胞中的细胞类型特异性剪接。使用 10 倍数据进行发现,具有可计算 SpliZ 分数的基因中有 9.1% 是细胞类型特异性剪接的,包括普遍表达的基因MYL6RPS24 。这些结果通过 RNA FISH、单细胞 PCR 和 Smart-seq2 进行了验证。 SpliZ 分析揭示了人类精子发生过程中 170 个剪接受调控的基因,其中包括小鼠和小鼠狐猴中保守的例子。 SpliZ 允许基于模型识别基于基因表达无法区分的亚群,这通过涉及SAT1中超保守外显子的经典单核细胞的亚群特异性剪接来说明。总之,对跨多个器官的差异剪接的分析证实剪接是细胞类型特异性调节的。
更新日期:2021-09-13
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