Steroid hormone receptors such as the Glucocorticoid Receptor (GR) mediate transcriptional responses to hormones and are frequently targeted in the treatment of human diseases. Experiments using bulk populations of cells have provided a detailed picture of the global transcriptional hormone response but are unable to interrogate cell-to-cell transcriptional heterogeneity. To examine the glucocorticoid response in individual cells, we performed single cell RNA sequencing (scRNAseq) in a human breast cancer cell line. The transcriptional response to hormone was robustly detected in individual cells and scRNAseq provided additional statistical power to identify over 100 GR-regulated genes that were not detected in bulk RNAseq. scRNAseq revealed striking cell-to-cell variability in the hormone response. On average, individual hormone-treated cells showed a response at only 30% of the total set of GR target genes. Understanding the basis of this heterogeneity will be critical for the development of more precise models of steroid hormone signaling.

类固醇激素受体（例如糖皮质激素受体（GR））介导对激素的转录反应，经常成为治疗人类疾病的靶标。使用大量细胞进行的实验提供了全局转录激素应答的详细图片，但无法询问细胞间转录异质性。为了检查单个细胞中的糖皮质激素反应，我们在人乳腺癌细胞系中进行了单细胞RNA测序（scRNAseq）。在单个细胞中可以强烈检测到对激素的转录反应，而scRNAseq提供了额外的统计能力，可以识别在大分子RNAseq中未检测到的100多个GR调控基因。scRNAseq在激素反应中显示出惊人的细胞间差异。一般，单独的激素处理细胞仅在全部GR靶基因的30％处显示出应答。了解这种异质性的基础对于开发更精确的类固醇激素信号传导模型至关重要。