Chromatin and Gene Expression Section, Epigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, Durham, NC, USA.
Integrative Bioinformatics, Epigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, Durham, NC, USA.
Commun Biol. 2020 Mar 13;3(1):126. doi: 10.1038/s42003-020-0837-0.
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.
甾体激素受体，如糖皮质激素受体 (GR)，介导激素的转录反应，并且经常被作为治疗人类疾病的靶点。使用细胞群体的实验提供了对全球转录激素反应的详细描述，但无法探究细胞间转录异质性。为了在单个细胞中检测糖皮质激素反应，我们在人类乳腺癌细胞系中进行了单细胞 RNA 测序 (scRNAseq)。在单个细胞中，激素反应被强烈地检测到，scRNAseq 提供了额外的统计能力，鉴定了超过 100 个在 bulk RNAseq 中未检测到的 GR 调节基因。scRNAseq 揭示了激素反应中惊人的细胞间变异性。平均而言，单个激素处理的细胞仅在总 GR 靶基因的 30%表现出反应。理解这种异质性的基础对于开发更精确的甾体激素信号模型至关重要。
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