Single cell RNA-seq data from: Differentiation signals induce APOBEC3A expression via GRHL3 in squamous epithelia and squamous cell carcinoma

Seurat object for single cell RNA-seq of 10 head and neck squamous cell carcinoma patients, epithelial cells only. From "Differentiation signals induce APOBEC3A expression via GRHL3 in squamous epithelia and squamous cell carcinoma ". Two APOBEC (apolipoprotein-B mRNA editing enzyme catalytic polypeptide-like) DNA cytosine deaminase enzymes (APOBEC3A and APOBEC3B) generate somatic mutations in cancer, driving tumour development and drug resistance. Here we used single cell RNA sequencing to study APOBEC3A and APOBEC3B expression in healthy and malignant mucosal epithelia, validating key observations with immunohistochemistry, spatial transcriptomics and functional experiments. Whereas APOBEC3B is expressed in keratinocytes entering mitosis, we show that APOBEC3A expression is confined largely to terminally differentiating cells and requires Grainyhead-like transcription factor 3 (GRHL3). Thus, in normal tissue, neither deaminase appears to be expressed at high levels during DNA replication, the cell cycle stage associated with APOBEC-mediated mutagenesis. In contrast, we show that in squamous cell carcinoma, there is expansion of GRHL3 expression and activity to a subset of cells undergoing DNA replication and concomitant extension of APOBEC3A expression to proliferating cells. These findings suggest that APOBEC3A may play a functional role during keratinocyte differentiation and offer a mechanism for acquisition of APOBEC3A mutagenic activity in tumours.用于10名头颈部鳞状细胞癌患者单细胞RNA测序分析的Seurat（Seurat）对象，仅包含上皮细胞。该数据集源自论文《分化信号通过Grainyhead样转录因子3（GRHL3）诱导鳞状上皮及鳞状细胞癌中APOBEC3A的表达》。两类载脂蛋白B mRNA编辑酶催化多肽样（APOBEC）DNA胞嘧啶脱氨酶——APOBEC3A与APOBEC3B——可在癌症中诱导体细胞突变，推动肿瘤发生与耐药性产生。本研究借助单细胞RNA测序技术，探究了健康黏膜上皮与恶性黏膜上皮中APOBEC3A及APOBEC3B的表达情况，并通过免疫组化、空间转录组学与功能实验验证了核心观测结果。尽管APOBEC3B在进入有丝分裂期的角质形成细胞中表达，但本研究发现APOBEC3A的表达主要局限于终末分化细胞，且其表达依赖于Grainyhead样转录因子3（GRHL3）。因此，在正常组织中，两类脱氨酶在DNA复制（与APOBEC介导的诱变相关的细胞周期阶段）期间均未呈现高表达。与之相反，在鳞状细胞癌中，GRHL3的表达与活性范围扩展至一部分正在进行DNA复制的细胞，同时APOBEC3A的表达也延伸至增殖细胞群体。上述研究结果表明，APOBEC3A可能在角质形成细胞分化过程中发挥功能性作用，并为肿瘤中APOBEC3A诱变活性的获得提供了潜在机制。