Dysregulated gene expressions of MEX3D, FOS and BCL2 in human induced-neuronal (iN) cells from NF1 patients: a pilot study.
Dysregulated gene expressions of MEX3D, FOS and BCL2 in human induced-neuronal (iN) cells from NF1 patients: a pilot study.
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DOI：
10.1038/s41598-017-14440-7
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发表时间：
2017-10-24
影响因子：
4.6
通讯作者：
Kanba S
中科院分区：
文献类型：
--
作者：
Sagata N;Kato TA;Kano SI;Ohgidani M;Shimokawa N;Sato-Kasai M;Hayakawa K;Kuwano N;Wilson AM;Ishizuka K;Kato S;Nakahara T;Nakahara-Kido M;Setoyama D;Sakai Y;Ohga S;Furue M;Sawa A;Kanba S
在2周内从人成纤维细胞产生诱导神经元（iN）细胞的直接转化技术有望发现神经精神疾病的未知神经元表型。在这里，我们提出了独特的基因表达谱的iN细胞从患者的神经纤维瘤病1型（NF 1），一个单基因多方面的疾病与自闭症谱系障碍（ASD）的并发症相对较高。对来自男性健康对照和男性NF 1患者的iN细胞（NF 1-iN细胞）的基于微阵列的转录组学分析显示，149个基因表达显著不同（110个上调，39个下调）。我们用12个性别混合的样本通过实时PCR验证了MEX 3D（mex-3 RNA结合家族成员D）的mRNA在NF 1-iN细胞中较低。在第14天的NF 1-iN细胞中，观察到FOS mRNA的较高表达，而MEX 3D mRNA的较低表达。有趣的是，BCL 2 mRNA在第5天（早期）在NF 1-iN细胞中较高，但在第14天不是。我们的数据表明，由于NF 1突变的异常分子信号可能会干扰基因表达，其中一个子集定义了连续的神经元表型的NF 1与ASD。需要进一步的翻译研究，使用诱导多能干（iPS）细胞衍生的神经元细胞，以验证我们的初步研究结果，特别是确认使用早期iN细胞分析的意义。
Direct conversion technique to produce induced-neuronal (iN) cells from human fibroblasts within 2 weeks is expected to discover unknown neuronal phenotypes of neuropsychiatric disorders. Here, we present unique gene expression profiles in iN cells from patients with neurofibromatosis type 1 (NF1), a single-gene multifaceted disorder with comparatively high co-occurrence of autism spectrum disorder (ASD). Microarray-based transcriptomic analysis on iN cells from male healthy controls and male NF1 patients (NF1-iN cells) revealed that 149 genes expressions were significantly different (110 upregulated and 39 downregulated). We validated that mRNA of MEX3D (mex-3 RNA binding family member D) was lower in NF1-iN cells by real-time PCR with 12 sex-mixed samples. In NF1-iN cells on day 14, higher expression of FOS mRNA was observed with lower expression of MEX3D mRNA. Interestingly, BCL2 mRNA was higher in NF1-iN cells on day 5 (early-period) but not on day 14. Our data suggest that aberrant molecular signals due to NF1 mutations may disturb gene expressions, a subset of which defines continuum of the neuronal phenotypes of NF1 with ASD. Further translational studies using induced pluripotent stem (iPS) cell-derived neuronal cells are needed to validate our preliminary findings especially confirming meanings of analysis using early-period iN cells.
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影响因子：
4
作者：
Hess, J;Angel, P;Schorpp-Kistner, M
通讯作者：
Schorpp-Kistner, M
神经元细胞的临床实用性直接从患者的成纤维细胞转化为神经精神疾病：溶酶体储存疾病和通道疗法的研究。
影响因子：
2.5
作者：
Kano S;Yuan M;Cardarelli RA;Maegawa G;Higurashi N;Gaval-Cruz M;Wilson AM;Tristan C;Kondo MA;Chen Y;Koga M;Obie C;Ishizuka K;Seshadri S;Srivastava R;Kato TA;Horiuchi Y;Sedlak TW;Lee Y;Rapoport JL;Hirose S;Okano H;Valle D;O'Donnell P;Sawa A;Kai M
通讯作者：
Kai M
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
2
作者：
Noll, Robert B.;Reiter-Purtill, Jennifer;Gerhardt, Cynthia A.
通讯作者：
Gerhardt, Cynthia A.
影响因子：
5.1
作者：
Johnson, NS;Saal, HM;Schorry, EK
通讯作者：
Schorry, EK