Transcriptional program of ciliated epithelial cells reveals new cilium and centrosome components and links to human disease.
Transcriptional program of ciliated epithelial cells reveals new cilium and centrosome components and links to human disease.
复制标题
DOI：
10.1371/journal.pone.0052166
复制
发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Stearns T
中科院分区：
文献类型：
--
作者：
Hoh RA;Stowe TR;Turk E;Stearns T
中心体和纤毛的缺陷与一系列具有不同表型的人类疾病相关。为了进一步表征定义这些细胞器功能的组分，我们确定了多纤毛气管上皮细胞的转录谱。在体外经历分化的小鼠气管上皮细胞的培养物来源于从纤毛细胞特异性FOXJ 1启动子（FOXJ 1：GFP）表达GFP的小鼠。在分化过程中的早期和晚期时间点确定来自这些培养物的纤毛GFP+细胞的转录谱，并通过减去非纤毛GFP-细胞的谱来细化。我们确定了649个基因在早期上调，当大多数细胞形成基体时，73个基因在晚期上调，当大多数细胞完全纤毛时。大多数，但不是全部，已知的中心体蛋白是转录上调早期，特别是Plk 4，一个主调节中心粒形成。我们发现，与人类疾病状态，Mdm 1，Mlf 1，和Dyx 1c 1，基因上调，在纤毛和本地化的中心粒和纤毛。哺乳动物多纤毛上皮细胞的转录组鉴定了新的候选中心体和纤毛蛋白，突出了能动纤毛和初级纤毛组分之间的相似性，并鉴定了纤毛蛋白与人类疾病之间的新联系。
Defects in the centrosome and cilium are associated with a set of human diseases having diverse phenotypes. To further characterize the components that define the function of these organelles we determined the transcriptional profile of multiciliated tracheal epithelial cells. Cultures of mouse tracheal epithelial cells undergoing differentiation in vitro were derived from mice expressing GFP from the ciliated-cell specific FOXJ1 promoter (FOXJ1:GFP). The transcriptional profile of ciliating GFP+ cells from these cultures was defined at an early and a late time point during differentiation and was refined by subtraction of the profile of the non-ciliated GFP- cells. We identified 649 genes upregulated early, when most cells were forming basal bodies, and 73 genes genes upregulated late, when most cells were fully ciliated. Most, but not all, of known centrosome proteins are transcriptionally upregulated early, particularly Plk4, a master regulator of centriole formation. We found that three genes associated with human disease states, Mdm1, Mlf1, and Dyx1c1, are upregulated during ciliogenesis and localize to centrioles and cilia. This transcriptome for mammalian multiciliated epithelial cells identifies new candidate centrosome and cilia proteins, highlights similarities between components of motile and primary cilia, and identifies new links between cilia proteins and human disease.
登录
查看更多内容
影响因子：
64.8
作者：
Dzhindzhev, Nikola S.;Yu, Quan D.;Glover, David M.
通讯作者：
Glover, David M.
DOI：
10.1083/jcb.201007107
发表时间：
2010-11-15
期刊：
The Journal of cell biology
影响因子：
--
作者：
Cizmecioglu O;Arnold M;Bahtz R;Settele F;Ehret L;Haselmann-Weiss U;Antony C;Hoffmann I
通讯作者：
Hoffmann I
影响因子：
3.5
作者：
Engelender, S;Sharp, AH;Ross, CA
通讯作者：
Ross, CA
影响因子：
64.8
作者：
Andersen, JS;Wilkinson, CJ;Mann, M
通讯作者：
Mann, M
影响因子：
9.2
作者：
Bettencourt-Dias, M;Rodrigues-Martins, A;Glover, DM
通讯作者：
Glover, DM