Habuka Masato, Fagerberg Linn, Hallström Björn M, Pontén Fredrik, Yamamoto Tadashi, Uhlen Mathias
Science for Life Laboratory, KTH - Royal Institute of Technology, SE-171 21, Stockholm, Sweden.
Department of Structural Pathology, Institute of Nephrology, Medical and Dental School, Niigata University, 1-757, Asahimachi-dori Niigata, 951-8510, Japan.
PLoS One. 2015 Dec 22;10(12):e0145301. doi: 10.1371/journal.pone.0145301. eCollection 2015.
To understand functions and diseases of urinary bladder, it is important to define its molecular constituents and their roles in urinary bladder biology. Here, we performed genome-wide deep RNA sequencing analysis of human urinary bladder samples and identified genes up-regulated in the urinary bladder by comparing the transcriptome data to those of all other major human tissue types. 90 protein-coding genes were elevated in the urinary bladder, either with enhanced expression uniquely in the urinary bladder or elevated expression together with at least one other tissue (group enriched). We further examined the localization of these proteins by immunohistochemistry and tissue microarrays and 20 of these 90 proteins were localized to the whole urothelium with a majority not yet described in the context of the urinary bladder. Four additional proteins were found specifically in the umbrella cells (Uroplakin 1a, 2, 3a, and 3b), and three in the intermediate/basal cells (KRT17, PCP4L1 and ATP1A4). 61 of the 90 elevated genes have not been previously described in the context of urinary bladder and the corresponding proteins are interesting targets for more in-depth studies. In summary, an integrated omics approach using transcriptomics and antibody-based profiling has been used to define a comprehensive list of proteins elevated in the urinary bladder.
为了解膀胱的功能和疾病,明确其分子组成成分及其在膀胱生物学中的作用至关重要。在此,我们对人类膀胱样本进行了全基因组深度RNA测序分析,并通过将转录组数据与所有其他主要人类组织类型的数据进行比较,鉴定出在膀胱中上调的基因。90个蛋白质编码基因在膀胱中表达升高,要么在膀胱中独特地增强表达,要么与至少一种其他组织一起表达升高(富集组)。我们通过免疫组织化学和组织微阵列进一步研究了这些蛋白质的定位,这90种蛋白质中有20种定位于整个尿路上皮,其中大多数在膀胱背景下尚未被描述。另外发现有4种蛋白质特异性存在于伞细胞中(uroplakin 1a、2、3a和3b),3种存在于中间/基底细胞中(KRT17、PCP4L1和ATP1A4)。90个上调基因中有61个此前在膀胱背景下未被描述,相应的蛋白质是更深入研究的有趣靶点。总之已采用一种结合转录组学和基于抗体的分析的综合组学方法来确定膀胱中升高的蛋白质的完整列表。