Molecular and cellular characterization of a zebrafish optic pathway tumor line implicates glia-derived progenitors in tumorigenesis.
Molecular and cellular characterization of a zebrafish optic pathway tumor line implicates glia-derived progenitors in tumorigenesis.
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DOI：
10.1371/journal.pone.0114888
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
McGrail M
中科院分区：
文献类型：
--
作者：
Solin SL;Wang Y;Mauldin J;Schultz LE;Lincow DE;Brodskiy PA;Jones CA;Syrkin-Nikolau J;Linn JM;Essner JJ;Hostetter JM;Whitley EM;Cameron JD;Chou HH;Severin AJ;Sakaguchi DS;McGrail M
在这项研究中，我们描述了斑马鱼突变体的分子和细胞特征，发展肿瘤的光学途径。杂合子Tg（flk 1：RFP）是18个转基因成人发生视网膜、视神经和视束肿瘤。分子和遗传图谱显示肿瘤表型与整合在3号染色体上的lincRNA基因lincRNAis 18/Zv9_00007276中的高拷贝数转基因阵列相关。TALEN用于分离去除lincRNAis 18基因的外显子2-5的147 kb缺失等位基因。缺失等位基因纯合子是可行的，不发展肿瘤，表明lincRNAis 18基因座的功能丧失不是肿瘤发作的触发因素。Tg（flk 1：RFP）18突变的视神经通路肿瘤在1岁时发生率为80-100%。视网膜肿瘤血管化程度高，由不同大小的视网膜细胞包埋在纤维基质中组成。免疫组化分析显示，胶质细胞标记物GFAP和BLBP在整个视网膜肿瘤和发育不良的视神经中的表达增加。我们对肿瘤前视网膜和视网膜肿瘤组织进行了转录组分析，发现放射状胶质细胞和星形胶质细胞（slc 1a 3）、活化胶质细胞（atf 3、blbp、apoeb）、增殖神经祖细胞（foxd 3、nestin、cdh 2、her 9/hes 1）和胶质瘤标志物（S100β、Vim）的基因表达特征发生了变化。转录组还显示cAMP、Stat 3和Wnt信号转导通路的激活。qRT-PCR证实Wnt途径组分hbegfa、ascl 1a和insm 1a的过表达>10倍。总之，这些数据表明Müller胶质细胞和/或星形胶质细胞衍生的祖细胞可能有助于斑马鱼Tg（flk 1：RFP）is 18视通路肿瘤。
In this study we describe the molecular and cellular characterization of a zebrafish mutant that develops tumors in the optic pathway. Heterozygous Tg(flk1:RFP)is18 transgenic adults develop tumors of the retina, optic nerve and optic tract. Molecular and genetic mapping demonstrate the tumor phenotype is linked to a high copy number transgene array integrated in the lincRNA gene lincRNAis18/Zv9_00007276 on chromosome 3. TALENs were used to isolate a 147kb deletion allele that removes exons 2–5 of the lincRNAis18 gene. Deletion allele homozygotes are viable and do not develop tumors, indicating loss of function of the lincRNAis18 locus is not the trigger for tumor onset. Optic pathway tumors in the Tg(flk1:RFP)is18 mutant occur with a penetrance of 80–100% by 1 year of age. The retinal tumors are highly vascularized and composed of rosettes of various sizes embedded in a fibrous matrix. Immunohistochemical analysis showed increased expression of the glial markers GFAP and BLBP throughout retinal tumors and in dysplastic optic nerve. We performed transcriptome analysis of pre-tumorous retina and retinal tumor tissue and found changes in gene expression signatures of radial glia and astrocytes (slc1a3), activated glia (atf3, blbp, apoeb), proliferating neural progenitors (foxd3, nestin, cdh2, her9/hes1), and glioma markers (S100β, vim). The transcriptome also revealed activation of cAMP, Stat3 and Wnt signal transduction pathways. qRT-PCR confirmed >10-fold overexpression of the Wnt pathway components hbegfa, ascl1a, and insm1a. Together the data indicate Müller glia and/or astrocyte-derived progenitors could contribute to the zebrafish Tg(flk1:RFP)is18 optic pathway tumors.
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影响因子：
3.4
作者：
Kassen, Sean C.;Thummel, Ryan;Hyde, David R.
通讯作者：
Hyde, David R.
影响因子：
3.7
作者：
McGrail M;Hatler JM;Kuang X;Liao HK;Nannapaneni K;Watt KE;Uhl JD;Largaespada DA;Vollbrecht E;Scheetz TE;Dupuy AJ;Hostetter JM;Essner JJ
通讯作者：
Essner JJ
DOI：
10.1073/pnas.1019012108
发表时间：
2011-09-20
影响因子：
11.1
作者：
Banerjee, Sutapa;Crouse, Nikkilina R.;Gutmann, David H.
通讯作者：
Gutmann, David H.
影响因子：
10.5
作者：
Kaul, Aparna;Chen, Yi-Hsien;Gutmann, David H.
通讯作者：
Gutmann, David H.
影响因子：
14.9
作者：
Doyle EL;Booher NJ;Standage DS;Voytas DF;Brendel VP;Vandyk JK;Bogdanove AJ
通讯作者：
Bogdanove AJ