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.

Details

Title
Dysregulated gene expressions of MEX3D, FOS and BCL2 in human induced-neuronal (iN) cells from NF1 patients: a pilot study
Author
Sagata, Noriaki 1 ; Kato, Takahiro A 1 ; Kano, Shin-ichi 2   VIAFID ORCID Logo  ; Ohgidani, Masahiro 1 ; Shimokawa, Norihiro 1 ; Sato-Kasai, Mina 1 ; Hayakawa, Kohei 1 ; Kuwano, Nobuki 1 ; Wilson, Ashley M 2 ; Ishizuka, Koko 2 ; Kato, Shiori 3 ; Nakahara, Takeshi 3 ; Nakahara-Kido, Makiko 3 ; Setoyama, Daiki 4 ; Sakai, Yasunari 5 ; Ohga, Shouichi 5 ; Furue, Masutaka 3 ; Sawa, Akira 2 ; Kanba, Shigenobu 1 

1  Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka, Japan 
2  Departments of Psychiatry, Mental Health, Neuroscience, and Biomedical Engineering, Johns Hopkins University School of Medicine and Bloomberg School of Public Health, 600 North Wolfe St., Baltimore, USA 
3  Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka, Japan 
4  Department of Clinical Chemistry and Laboratory Medicine, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka, Japan 
5  Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka, Japan 
Pages
1-8
Publication year
2017
Publication date
Oct 2017
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41598-017-14440-7
ProQuest document ID
1955029955
Copyright
© 2017. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.