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

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

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Abstract

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.

Original languageEnglish
Article number13905
JournalScientific reports
Volume7
Issue number1
DOIs
Publication statusPublished - Dec 1 2017

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Neurofibromatosis 1
Gene Expression
Messenger RNA
Phenotype
Induced Pluripotent Stem Cells
Transcriptome
Real-Time Polymerase Chain Reaction
Down-Regulation
Fibroblasts
RNA
Mutation

All Science Journal Classification (ASJC) codes

  • General

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

In: Scientific reports, Vol. 7, No. 1, 13905, 01.12.2017.

Research output: Contribution to journalArticle

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 2017, 'Dysregulated gene expressions of MEX3D, FOS and BCL2 in human induced-neuronal (iN) cells from NF1 patients: A pilot study', Scientific reports, vol. 7, no. 1, 13905. https://doi.org/10.1038/s41598-017-14440-7
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. / Dysregulated gene expressions of MEX3D, FOS and BCL2 in human induced-neuronal (iN) cells from NF1 patients : A pilot study. In: Scientific reports. 2017 ; Vol. 7, No. 1.
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AU - Sagata, Noriaki

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AU - Kano, Shin Ichi

AU - Ohgidani, Masahiro

AU - Shimokawa, Norihiro

AU - Sato-Kasai, Mina

AU - Hayakawa, Kohei

AU - Kuwano, Nobuki

AU - Wilson, Ashley M.

AU - Ishizuka, Koko

AU - Kato, Shiori

AU - Nakahara, Takeshi

AU - Nakahara-Kido, Makiko

AU - Setoyama, Daiki

AU - Sakai, Yasunari

AU - Ohga, Shouichi

AU - Furue, Masutaka

AU - Sawa, Akira

AU - Kanba, Shigenobu

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