Zhang Dingxiao, Park Daechan, Zhong Yi, Lu Yue, Rycaj Kiera, Gong Shuai, Chen Xin, Liu Xin, Chao Hsueh-Ping, Whitney Pamela, Calhoun-Davis Tammy, Takata Yoko, Shen Jianjun, Iyer Vishwanath R, Tang Dean G
Department of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Smithville, 78957 Texas, USA.
Department of Molecular Biosciences, Institute for Cellular and Molecular Biology, Center for Systems and Synthetic Biology, University of Texas at Austin, Austin, 78712 Texas, USA.
Nat Commun. 2016 Feb 29;7:10798. doi: 10.1038/ncomms10798.
The prostate gland mainly contains basal and luminal cells constructed as a pseudostratified epithelium. Annotation of prostate epithelial transcriptomes provides a foundation for discoveries that can impact disease understanding and treatment. Here we describe a genome-wide transcriptome analysis of human benign prostatic basal and luminal epithelial populations using deep RNA sequencing. Through molecular and biological characterizations, we show that the differential gene-expression profiles account for their distinct functional properties. Strikingly, basal cells preferentially express gene categories associated with stem cells, neurogenesis and ribosomal RNA (rRNA) biogenesis. Consistent with this profile, basal cells functionally exhibit intrinsic stem-like and neurogenic properties with enhanced rRNA transcription activity. Of clinical relevance, the basal cell gene-expression profile is enriched in advanced, anaplastic, castration-resistant and metastatic prostate cancers. Therefore, we link the cell-type-specific gene signatures to aggressive subtypes of prostate cancer and identify gene signatures associated with adverse clinical features.
前列腺主要包含构建为假复层上皮的基底细胞和管腔细胞。前列腺上皮转录组的注释为可能影响疾病理解和治疗的发现奠定了基础。在此，我们使用深度RNA测序描述了人类良性前列腺基底和管腔上皮细胞群体的全基因组转录组分析。通过分子和生物学特征分析，我们表明差异基因表达谱解释了它们不同的功能特性。引人注目的是，基底细胞优先表达与干细胞、神经发生和核糖体RNA（rRNA）生物合成相关的基因类别。与此特征一致，基底细胞在功能上表现出内在的干细胞样和神经源性特性，并具有增强的rRNA转录活性。具有临床相关性的是，基底细胞基因表达谱在晚期、间变性、去势抵抗性和转移性前列腺癌中富集。因此，我们将细胞类型特异性基因特征与前列腺癌的侵袭性亚型联系起来，并鉴定出与不良临床特征相关的基因特征。
