Transcriptome comparison of human neurons generated using induced pluripotent stem cells derived from dental pulp and skin fibroblasts.
Transcriptome comparison of human neurons generated using induced pluripotent stem cells derived from dental pulp and skin fibroblasts.
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DOI：
10.1371/journal.pone.0075682
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Lachman HM
中科院分区：
文献类型：
--
作者：
Chen J;Lin M;Foxe JJ;Pedrosa E;Hrabovsky A;Carroll R;Zheng D;Lachman HM
诱导多能干细胞（iPSC）技术通过在体外培养患者特异性神经元的能力，为研究神经精神疾病提供了机会。通过活检获得的皮肤成纤维细胞一直是重编程最可靠的细胞来源。然而，使用通过侵入性较小的方法获得的其他体细胞将是理想的，特别是在患有自闭症谱系障碍（ASD）和其他神经发育疾病的儿童中。除了成纤维细胞之外，iPSC已经从脐带血、淋巴细胞、毛发角质形成细胞和来自乳牙的牙髓中开发。其中，牙髓将是儿童神经发育障碍的良好来源，因为获得材料是非侵入性的。我们通过使用RNA-seq对从乳牙牙髓提取的iPSC（T-iPSC）和成纤维细胞（F-iPSC）制成的分化神经元进行基因表达谱分析，研究了其对疾病建模的适用性。这是第一个RNA-seq分析，比较了来自不同体细胞的iPSC的神经元中的基因表达谱。在大多数情况下，基因表达谱非常相似，只有329个基因在名义上显著的p值（p<0.05）下显示出差异表达，其中63个在校正全基因组分析后仍然显著（FDR <0.05）。最显著的差异是在来自T-iPSC的神经元中检测到所有四个HOX基因家族的许多成员的表达水平较低。此外，在发育中的前脑中表达的几种转录因子（例如FOXP 2，OTX 1和LHX 2）的表达水平增加。总体而言，通路分析揭示了在源自T-iPSC的神经元中显示出较高表达水平的差异表达基因富集了与精神分裂症（SZ）有关的基因。这些发现表明，来自T-iPSCs的神经元适合于疾病建模神经精神疾病，并且可能比来自F-iPSCs的神经元具有一些优势。
Induced pluripotent stem cell (iPSC) technology is providing an opportunity to study neuropsychiatric disorders through the capacity to grow patient-specific neurons in vitro. Skin fibroblasts obtained by biopsy have been the most reliable source of cells for reprogramming. However, using other somatic cells obtained by less invasive means would be ideal, especially in children with autism spectrum disorders (ASD) and other neurodevelopmental conditions. In addition to fibroblasts, iPSCs have been developed from cord blood, lymphocytes, hair keratinocytes, and dental pulp from deciduous teeth. Of these, dental pulp would be a good source for neurodevelopmental disorders in children because obtaining material is non-invasive. We investigated its suitability for disease modeling by carrying out gene expression profiling, using RNA-seq, on differentiated neurons derived from iPSCs made from dental pulp extracted from deciduous teeth (T-iPSCs) and fibroblasts (F-iPSCs). This is the first RNA-seq analysis comparing gene expression profiles in neurons derived from iPSCs made from different somatic cells. For the most part, gene expression profiles were quite similar with only 329 genes showing differential expression at a nominally significant p-value (p<0.05), of which 63 remained significant after correcting for genome-wide analysis (FDR <0.05). The most striking difference was the lower level of expression detected for numerous members of the all four HOX gene families in neurons derived from T-iPSCs. In addition, an increased level of expression was seen for several transcription factors expressed in the developing forebrain (FOXP2, OTX1, and LHX2, for example). Overall, pathway analysis revealed that differentially expressed genes that showed higher levels of expression in neurons derived from T-iPSCs were enriched for genes implicated in schizophrenia (SZ). The findings suggest that neurons derived from T-iPSCs are suitable for disease-modeling neuropsychiatric disorder and may have some advantages over those derived from F-iPSCs.
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影响因子：
5.3
作者：
Casey JP;Magalhaes T;Conroy JM;Regan R;Shah N;Anney R;Shields DC;Abrahams BS;Almeida J;Bacchelli E;Bailey AJ;Baird G;Battaglia A;Berney T;Bolshakova N;Bolton PF;Bourgeron T;Brennan S;Cali P;Correia C;Corsello C;Coutanche M;Dawson G;de Jonge M;Delorme R;Duketis E;Duque F;Estes A;Farrar P;Fernandez BA;Folstein SE;Foley S;Fombonne E;Freitag CM;Gilbert J;Gillberg C;Glessner JT;Green J;Guter SJ;Hakonarson H;Holt R;Hughes G;Hus V;Igliozzi R;Kim C;Klauck SM;Kolevzon A;Lamb JA;Leboyer M;Le Couteur A;Leventhal BL;Lord C;Lund SC;Maestrini E;Mantoulan C;Marshall CR;McConachie H;McDougle CJ;McGrath J;McMahon WM;Merikangas A;Miller J;Minopoli F;Mirza GK;Munson J;Nelson SF;Nygren G;Oliveira G;Pagnamenta AT;Papanikolaou K;Parr JR;Parrini B;Pickles A;Pinto D;Piven J;Posey DJ;Poustka A;Poustka F;Ragoussis J;Roge B;Rutter ML;Sequeira AF;Soorya L;Sousa I;Sykes N;Stoppioni V;Tancredi R;Tauber M;Thompson AP;Thomson S;Tsiantis J;Van Engeland H;Vincent JB;Volkmar F;Vorstman JA;Wallace S;Wang K;Wassink TH;White K;Wing K;Wittemeyer K;Yaspan BL;Zwaigenbaum L;Betancur C;Buxbaum JD;Cantor RM;Cook EH;Coon H;Cuccaro ML;Geschwind DH;Haines JL;Hallmayer J;Monaco AP;Nurnberger JI Jr;Pericak-Vance MA;Schellenberg GD;Scherer SW;Sutcliffe JS;Szatmari P;Vieland VJ;Wijsman EM;Green A;Gill M;Gallagher L;Vicente A;Ennis S
通讯作者：
Ennis S
影响因子：
3.3
作者：
Beltrao-Braga, Patricia C. B.;Pignatari, Graciela C.;Kerkis, Irina
通讯作者：
Kerkis, Irina
影响因子：
46.9
作者：
Danwei Huangfu;Osafune, Kenji;Melton, Douglas A.
通讯作者：
Melton, Douglas A.
影响因子：
15.1
作者：
Lei JX;Cassone CG;Luebbert C;Liu QY
通讯作者：
Liu QY
影响因子：
2.5
作者：
DeRosa BA;Van Baaren JM;Dubey GK;Lee JM;Cuccaro ML;Vance JM;Pericak-Vance MA;Dykxhoorn DM
通讯作者：
Dykxhoorn DM