Details

Autor(en) / Beteiligte

• Sagata, Noriaki
• Kato, Takahiro A
• Kano, Shin-Ichi
• Ohgidani, Masahiro
• Shimokawa, Norihiro
• Sato-Kasai, Mina
• Hayakawa, Kohei
• Kuwano, Nobuki
• Wilson, Ashley M
• Ishizuka, Koko
• Kato, Shiori
• Nakahara, Takeshi
• Nakahara-Kido, Makiko
• Setoyama, Daiki
• Sakai, Yasunari
• Ohga, Shouichi
• Furue, Masutaka
• Sawa, Akira
• Kanba, Shigenobu

Titel

Dysregulated gene expressions of MEX3D, FOS and BCL2 in human induced-neuronal (iN) cells from NF1 patients: a pilot study

Ist Teil von

• Scientific reports, 2017-10, Vol.7 (1), p.13905-8, Article 13905

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2017

Link zum Volltext

Quelle

EZB Free E-Journals

Beschreibungen/Notizen

• 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.