GSE135769
Single Cell RNA-Seq Reveals Changing Landscape of Cell-to-Cell Variation Induced by CTCF Knockdown
In this study, we knockdown the expression of CTCF in EL4 cells by shRNA, followed by single cell RNA-seq on both wild type (WT) cells and CTCF-Knockdown (CTCF-KD) cells. Principal component analysis (PCA) of single cell RNA-seq data showed that WT cells and CTCF-KD cells essentially concentrated in two different clusters on the PCA projection, indicating gene expression profiles of CTCF-KD cells and WT cells were systematically different. We further found the cells' CTCF expression levels were correlated with the cell's positioning on PCA projection. Interestingly, GO terms including regulation of transcription, DNA binding, Zinc finger and transcription factor binding are significantly enriched in CTCF-KD specific highly variable genes, indicating tissue specific genes such as transcription factors were highly sensitive to CTCF-KD level and showed strongly increased variation. While the housekeeping genes including rRNA processing, DNA repair and tRNA processing are significantly enriched in WT specific highly variable genes, potentially indicating cell-to-cell variation of cell activity in WT cells is higher than that of CTCF-KD cells. We found CTCF-KD cell specific highly variable genes were significantly enriched in CTCF-KD specific down-regulated genes, indicating knockdown of CTCF simultaneously reduced expression levels and increased gene expression noises of its target genes. In summary, analysis of genome-wide cell-to-cell variation in this study showed CTCF-medicated promoter-enhancer interaction not only important for maintaining the expression of its target genes, but also played important roles in reducing the expression noise of its target genes. Overall design: In this study, we knockdown the expression of CTCF in EL4 cells by shRNA, followed by single cell RNA-seq on both wild type (WT) cells and CTCF-Knockdown (CTCF-KD) cells. To identify the influence of CTCF on genome-wide landscape of cell-to-cell variations.