RNA-Seq of human neurons derived from iPS cells reveals candidate long non-coding RNAs involved in neurogenesis and neuropsychiatric disorders.
RNA-Seq of human neurons derived from iPS cells reveals candidate long non-coding RNAs involved in neurogenesis and neuropsychiatric disorders.
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DOI：
10.1371/journal.pone.0023356
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发表时间：
2011
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：
Lin M;Pedrosa E;Shah A;Hrabovsky A;Maqbool S;Zheng D;Lachman HM
使用下一代测序（RNA-Seq）的全基因组表达分析提供了对基本生物过程（例如细胞分化和恶性转化）进行深入分子分析的机会。从诱导多能干细胞（iPSC）衍生的分化的人类神经元为RNA-Seq提供了理想的系统，因为由转录因子、DNA甲基化和染色质修饰剂的异常引起的神经发生缺陷是一些神经精神疾病的核心。作为使用源自患者特异性iPSC的神经元应用下一代测序的初步步骤，我们对对照人类神经元进行了RNA-Seq分析。在从多能干细胞到早期分化神经元的过渡过程中，编码基因、长链非编码RNA（lncRNA）、假基因和剪接异构体的表达发生了巨大变化。在这种转变期间经历表达的根本变化的许多基因包括精神分裂症（SZ）、双相情感障碍（BD）和自闭症谱系障碍（ASD）的候选者，其充当转录因子和染色质修饰剂，如POU 3F 2和ZNF 804 A，以及编码与这些病症有关的细胞粘附蛋白的基因，包括NRXN 1和NLGN 1。此外，发现许多新的lncRNA的表达发生了显着变化，其中之一是HOTAIRM 1，在骨髓生成过程中的几个HOXA基因的调节因子。我们在分化神经元中观察到的增加也表明了在神经发生中的作用。最后，在全基因组关联研究中与SZ相关的SNP附近的几种lncRNA在神经元分化期间也增加，表明这些新的转录物可能在患者亚组中受到异常调节。
Genome-wide expression analysis using next generation sequencing (RNA-Seq) provides an opportunity for in-depth molecular profiling of fundamental biological processes, such as cellular differentiation and malignant transformation. Differentiating human neurons derived from induced pluripotent stem cells (iPSCs) provide an ideal system for RNA-Seq since defective neurogenesis caused by abnormalities in transcription factors, DNA methylation, and chromatin modifiers lie at the heart of some neuropsychiatric disorders. As a preliminary step towards applying next generation sequencing using neurons derived from patient-specific iPSCs, we have carried out an RNA-Seq analysis on control human neurons. Dramatic changes in the expression of coding genes, long non-coding RNAs (lncRNAs), pseudogenes, and splice isoforms were seen during the transition from pluripotent stem cells to early differentiating neurons. A number of genes that undergo radical changes in expression during this transition include candidates for schizophrenia (SZ), bipolar disorder (BD) and autism spectrum disorders (ASD) that function as transcription factors and chromatin modifiers, such as POU3F2 and ZNF804A, and genes coding for cell adhesion proteins implicated in these conditions including NRXN1 and NLGN1. In addition, a number of novel lncRNAs were found to undergo dramatic changes in expression, one of which is HOTAIRM1, a regulator of several HOXA genes during myelopoiesis. The increase we observed in differentiating neurons suggests a role in neurogenesis as well. Finally, several lncRNAs that map near SNPs associated with SZ in genome wide association studies also increase during neuronal differentiation, suggesting that these novel transcripts may be abnormally regulated in a subgroup of patients.
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DOI：
10.1002/ajmg.b.31063
发表时间：
2010-06-05
影响因子：
2.8
作者：
Ching, Michael S. L.;Shen, Yiping;Tan, Wen-Hann;Jeste, Shafali S.;Morrow, Eric M.;Chen, Xiaoli;Mukaddes, Nahit M.;Yoo, Seung-Yun;Hanson, Ellen;Hundley, Rachel;Austin, Christina;Becker, Ronald E.;Berry, Gerard T.;Driscoll, Katherine;Engle, Elizabeth C.;Friedman, Sandra;Gusella, James F.;Hisama, Fuki M.;Irons, Mira B.;Lafiosca, Tina;LeClair, Elaine;Miller, David T.;Neessen, Michael;Picker, Jonathan D.;Rappaport, Leonard;Rooney, Cynthia M.;Sarco, Dean P.;Stoler, Joan M.;Walsh, Christopher A.;Wolff, Robert R.;Zhang, Ting;Nasir, Ramzi H.;Wu, Bai-Lin
通讯作者：
Wu, Bai-Lin
影响因子：
3.3
作者：
Barnett, J. H.;Smoller, J. W.
通讯作者：
Smoller, J. W.
影响因子：
64.8
作者：
通讯作者：
--
DOI：
10.1186/1477-7827-9-50
发表时间：
2011-04-16
期刊：
Reproductive biology and endocrinology : RB&E
影响因子：
--
作者：
Alekseev OM;Richardson RT;Tsuruta JK;O'Rand MG
通讯作者：
O'Rand MG
影响因子：
4
作者：
Butler, John T.;Hall, Lisa L.;Smith, Kelly P.;Lawrence, Jeanne B.
通讯作者：
Lawrence, Jeanne B.