Forskolin rapidly enhances neuron-like morphological change of directly induced-neuronal cells from neurofibromatosis type 1 patients.
Forskolin rapidly enhances neuron-like morphological change of directly induced-neuronal cells from neurofibromatosis type 1 patients.
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DOI：
10.1002/npr2.12144
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发表时间：
2020-12
影响因子：
2.5
通讯作者：
Kato TA
中科院分区：
文献类型：
--
作者：
Sagata N;Kano SI;Ohgidani M;Inamine S;Sakai Y;Kato H;Masuda K;Nakahara T;Nakahara-Kido M;Ohga S;Furue M;Sawa A;Kanba S;Kato TA
1 型神经纤维瘤病 (NF1) 是一种多方面的疾病，经常与自闭症谱系障碍 (ASD) 和学习障碍等神经发育障碍共存。腺苷酸环化酶（AC）功能障碍是NF1患者脑部神经细胞发育异常的候选途径之一，但其动态异常尚未观察到。直接转化技术可以在 2 周内直接从人类成纤维细胞生成诱导神经元 (iN) 细胞。最近，我们发现毛喉素（一种 AC 激活剂）可以挽救 NF1 患者来源的 iN 细胞（NF1-iN 细胞）的基因表达模式。在这份微报告中，我们展示了毛喉素对 NF1-iN 细胞的动态影响。来自健康对照的 iN 细胞（HC-iN 细胞）和 NF1-iN 细胞分别用毛喉素（终浓度 10 μM）处理。带有 CCD 相机的倒置显微镜每 2 分钟捕捉一次 iN 细胞的形态变化，持续 90 分钟。在毛喉素治疗之前，在 HC-iN 细胞中观察到神经元样球形细胞，但大多数 NF1-iN 细胞不是球形而是扁平形。毛喉素处理后仅 20 分钟，iN 细胞的形态就从扁平状显着改变为球形，特别是在 NF1-iN 细胞中。目前的试验数据表明，毛喉素或 AC 激活剂可能对 NF1 患者神经元细胞的生长具有治疗作用。应进行进一步的转化研究，以验证我们未来 ASD 药物开发的试点结果。 1 型神经纤维瘤病 (NF1) 与自闭症谱系障碍 (ASD) 和学习障碍等神经发育障碍高度共存，其潜在机制尚未明确。我们在此表明，毛喉素（一种 AC 激活剂）可快速增强来自 NF1 患者的直接诱导神经元 (iN) 细胞的神经元样形态变化。目前使用直接转换技术的试验数据表明，毛喉素或 AC 激活剂可能对 NF1 患者神经元细胞的生长具有治疗作用。
Neurofibromatosis type 1 (NF1) is a multifaceted disease, and frequently comorbid with neurodevelopmental disorders such as autism spectrum disorder (ASD) and learning disorder. Dysfunction of adenylyl cyclase (AC) is one of the candidate pathways in abnormal development of neuronal cells in the brain of NF1 patients, while its dynamic abnormalities have not been observed. Direct conversion technology can generate induced‐neuronal (iN) cells directly from human fibroblasts within 2 weeks. Just recently, we have revealed that forskolin, an AC activator, rescues the gene expression pattern of iN cells derived from NF1 patients (NF1‐iN cells). In this microreport, we show the dynamic effect of forskolin on NF1‐iN cells. iN cells derived from healthy control (HC‐iN cells) and NF1‐iN cells were treated with forskolin (final concentration 10 μM), respectively. Morphological changes of iN cells were captured by inverted microscope with CCD camera every 2 minutes for 90 minutes. Prior to forskolin treatment, neuron‐like spherical‐form cells were observed in HC‐iN cells, but most NF1‐iN cells were not spherical‐form but flatform. Only 20 minutes after forskolin treatment, the morphology of the iN cells were dramatically changed from flatform to spherical form, especially in NF1‐iN cells. The present pilot data indicate that forskolin or AC activators may have therapeutic effects on the growth of neuronal cells in NF1 patients. Further translational research should be conducted to validate our pilot findings for future drug development of ASD. Neurofibromatosis type 1 (NF1) is highly comorbid with neurodevelopmental disorders such as autism spectrum disorder (ASD) and learning disorder, and underlying mechanisms have not been well clarified. We herein showed that forskolin, an AC activator, rapidly enhances neuron‐like morphological change of directly induced‐neuronal (iN) cells from NF1 patients. The present pilot data using the direct conversion technology indicate that forskolin or AC activators may have therapeutic effects on the growth of neuronal cells in NF1 patients.
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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
通过确定的因素将成纤维细胞直接转化为功能性神经元。
影响因子：
64.8
作者：
Vierbuchen, Thomas;Ostermeier, Austin;Pang, Zhiping P.;Kokubu, Yuko;Suedhof, Thomas C.;Wernig, Marius
通讯作者：
Wernig, Marius
影响因子：
5.1
作者：
Johnson, NS;Saal, HM;Schorry, EK
通讯作者：
Schorry, EK
影响因子：
2.9
作者：
Passeri, Eleonora;Wilson, Ashley M.;Ishizuka, Koko
通讯作者：
Ishizuka, Koko
影响因子：
4.7
作者：
Ishitani, Tohru;Ishitani, Shizuka;Itoh, Motoyuki
通讯作者：
Itoh, Motoyuki