Intrinsic androgen-dependent gene expression patterns revealed by comparison of genital fibroblasts from normal males and individuals with complete and partial androgen insensitivity syndrome.
Intrinsic androgen-dependent gene expression patterns revealed by comparison of genital fibroblasts from normal males and individuals with complete and partial androgen insensitivity syndrome.
复制标题
DOI：
10.1186/1471-2164-8-376
复制
发表时间：
2007-10-18
期刊：
影响因子：
4.4
通讯作者：
Brooks JD
中科院分区：
文献类型：
--
作者：
Holterhus PM;Deppe U;Werner R;Richter-Unruh A;Bebermeier JH;Wünsch L;Krege S;Schweikert HU;Demeter J;Riepe F;Hiort O;Brooks JD
为了更好地理解正常和异常生殖器发育的分子程序，需要明确定义雄激素依赖性基因表达模式，而不受基因型（46，XX vs. 46，XY）的影响。以前，我们已经确定了生殖器来源的成纤维细胞的全球基因表达谱，不同的46，XY男性和46，XY女性完全雄激素不敏感综合征（CAIS）由于失活突变的雄激素受体（AR）。虽然这些差异可能是由于雄激素编程诱导的基因表达的细胞自主变化，但最近的研究表明，它们也可能受到收获成纤维细胞的位置（拓扑学）的影响。为了最大限度地减少拓扑结构的影响，我们比较了来自相同泌尿生殖器原基的成纤维细胞的基因表达模式：正常男性化的46，XY男性的阴囊和完全女性化的46，XY CAIS个体的大阴唇。代表440个独特基因的612个转录本在阴囊和CAIS大阴唇之间的表达水平存在显著差异，表明雄激素编程的影响。虽然有些基因与我们以前鉴定的基因（TBX3，IGFBP5，EGFR，CSPG2）一致，但有相当数量的基因不一致，这意味着拓扑结构影响了我们以前实验中的基因表达。来自部分AIS个体的大量成纤维细胞培养物的基因表达数据的监督聚类显示，新的拓扑控制数据集更好地对标本进行分类。AR本身的失活突变似乎诱导培养的成纤维细胞中基因表达的持久变化，与拓扑结构和基因型无关。基因鉴定可能是相关的候选人破译雄激素依赖的正常和异常生殖器发育。
To better understand the molecular programs of normal and abnormal genital development, clear-cut definition of androgen-dependent gene expression patterns, without the influence of genotype (46, XX vs. 46, XY), is warranted. Previously, we have identified global gene expression profiles in genital-derived fibroblasts that differ between 46, XY males and 46, XY females with complete androgen insensitivity syndrome (CAIS) due to inactivating mutations of the androgen receptor (AR). While these differences could be due to cell autonomous changes in gene expression induced by androgen programming, recent work suggests they could also be influenced by the location from which the fibroblasts were harvested (topology). To minimize the influence of topology, we compared gene expression patterns of fibroblasts derived from identical urogenital anlagen: the scrotum in normally virilized 46, XY males and the labia majora from completely feminized 46, XY individuals with CAIS. 612 transcripts representing 440 unique genes differed significantly in expression levels between scrotum and CAIS labia majora, suggesting the effects of androgen programming. While some genes coincided with those we had identified previously (TBX3, IGFBP5, EGFR, CSPG2), a significant number did not, implying that topology had influenced gene expression in our previous experiments. Supervised clustering of gene expression data derived from a large set of fibroblast cultures from individuals with partial AIS revealed that the new, topology controlled data set better classified the specimens. Inactivating mutations of the AR, in themselves, appear to induce lasting changes in gene expression in cultured fibroblasts, independent of topology and genotype. Genes identified are likely to be relevant candidates to decipher androgen-dependent normal and abnormal genital development.
登录
查看更多内容
DOI：
10.1073/pnas.091062498
发表时间：
2001-04-24
影响因子：
11.1
作者：
Tusher, VG;Tibshirani, R;Chu, G
通讯作者：
Chu, G
DOI：
10.1016/j.biocel.2003.12.002
发表时间：
2004-06-01
影响因子：
4
作者：
Chiquet-Ehrismann, R
通讯作者：
Chiquet-Ehrismann, R
影响因子：
158.5
作者：
Bullinger, L;Döhner, K;Pollack, JR
通讯作者：
Pollack, JR
影响因子：
20.3
作者：
QUIGLEY, CA;DEBELLIS, A;FRENCH, FS
通讯作者：
FRENCH, FS
影响因子：
5.3
作者：
WILSON, JD;GRIFFIN, JE;GEORGE, FW
通讯作者：
GEORGE, FW