Transcriptome analysis of genetically matched human induced pluripotent stem cells disomic or trisomic for chromosome 21.
Transcriptome analysis of genetically matched human induced pluripotent stem cells disomic or trisomic for chromosome 21.
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DOI：
10.1371/journal.pone.0194581
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Link CD
中科院分区：
文献类型：
--
作者：
Gonzales PK;Roberts CM;Fonte V;Jacobsen C;Stein GH;Link CD
21号染色体三体是唐氏综合症的遗传原因，它有可能改变21号染色体上基因的表达，以及整个基因组的其他位置。这些转录组的变化可能是唐氏综合症临床表型的基础。我们已经使用RNA-SEQ对21号染色体三体引起的转录组变化进行了深入的分析，使用了来自单个唐氏综合症患者的诱导多能干细胞(IPSCs)。这些细胞最初是由Li等人衍生出来的，他们在基因上以三体IPSC中的21号染色体为靶点，允许选择二体同胞IPSC克隆。对维持为IPSCs或分化为皮质神经元培养的三体/二体细胞对进行分析。除了基因表达水平的特征外，我们还研究了RNA腺苷到肌苷的编辑、选择性剪接和重复元件表达的模式，这些方面的转录组在唐氏综合症的背景下还没有显著的特征。我们发现了与21号染色体三体相关的转录积累的显著变化，以及选择性剪接和重复元件转录本的变化。出乎意料的是，与另一项研究相反，我们描述的三体IPSCs比对照二体IPSCs表达更高水平的神经元转录，并容易分化为皮质神经元。将我们的转录组数据与三体IPSCs的类似研究进行比较，表明21号染色体的三体可能不会从本质上限制神经元的分化，而是可能干扰多能性的维持。
Trisomy of chromosome 21, the genetic cause of Down syndrome, has the potential to alter expression of genes on chromosome 21, as well as other locations throughout the genome. These transcriptome changes are likely to underlie the Down syndrome clinical phenotypes. We have employed RNA-seq to undertake an in-depth analysis of transcriptome changes resulting from trisomy of chromosome 21, using induced pluripotent stem cells (iPSCs) derived from a single individual with Down syndrome. These cells were originally derived by Li et al, who genetically targeted chromosome 21 in trisomic iPSCs, allowing selection of disomic sibling iPSC clones. Analyses were conducted on trisomic/disomic cell pairs maintained as iPSCs or differentiated into cortical neuronal cultures. In addition to characterization of gene expression levels, we have also investigated patterns of RNA adenosine-to-inosine editing, alternative splicing, and repetitive element expression, aspects of the transcriptome that have not been significantly characterized in the context of Down syndrome. We identified significant changes in transcript accumulation associated with chromosome 21 trisomy, as well as changes in alternative splicing and repetitive element transcripts. Unexpectedly, the trisomic iPSCs we characterized expressed higher levels of neuronal transcripts than control disomic iPSCs, and readily differentiated into cortical neurons, in contrast to another reported study. Comparison of our transcriptome data with similar studies of trisomic iPSCs suggests that trisomy of chromosome 21 may not intrinsically limit neuronal differentiation, but instead may interfere with the maintenance of pluripotency.
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影响因子：
4.4
作者：
Ling KH;Hewitt CA;Tan KL;Cheah PS;Vidyadaran S;Lai MI;Lee HC;Simpson K;Hyde L;Pritchard MA;Smyth GK;Thomas T;Scott HS
通讯作者：
Scott HS
影响因子：
4.7
作者：
Potier, MC;Rivals, I;Dauphinot, L
通讯作者：
Dauphinot, L
影响因子：
14.9
作者：
Hartley SW;Mullikin JC
通讯作者：
Mullikin JC
DOI：
10.1002/ajmg.a.37156
发表时间：
2015-09
期刊：
American journal of medical genetics. Part A
影响因子：
--
作者：
Guedj F;Pennings JL;Ferres MA;Graham LC;Wick HC;Miczek KA;Slonim DK;Bianchi DW
通讯作者：
Bianchi DW
影响因子：
16.2
作者：
Olmos-Serrano JL;Kang HJ;Tyler WA;Silbereis JC;Cheng F;Zhu Y;Pletikos M;Jankovic-Rapan L;Cramer NP;Galdzicki Z;Goodliffe J;Peters A;Sethares C;Delalle I;Golden JA;Haydar TF;Sestan N
通讯作者：
Sestan N