論文

査読有り 筆頭著者 国際誌
2020年7月

Dyslexia Candidate Gene and Ciliary Gene Expression Dynamics During Human Neuronal Differentiation.

Molecular neurobiology
  • Andrea Bieder
  • ,
  • Masahito Yoshihara
  • ,
  • Shintaro Katayama
  • ,
  • Kaarel Krjutškov
  • ,
  • Anna Falk
  • ,
  • Juha Kere
  • ,
  • Isabel Tapia-Páez

57
7
開始ページ
2944
終了ページ
2958
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1007/s12035-020-01905-6

Developmental dyslexia (DD) is a neurodevelopmental condition with complex genetic mechanisms. A number of candidate genes have been identified, some of which are linked to neuronal development and migration and to ciliary functions. However, expression and regulation of these genes in human brain development and neuronal differentiation remain uncharted. Here, we used human long-term self-renewing neuroepithelial stem (lt-NES, here termed NES) cells derived from human induced pluripotent stem cells to study neuronal differentiation in vitro. We characterized gene expression changes during differentiation by using RNA sequencing and validated dynamics for selected genes by qRT-PCR. Interestingly, we found that genes related to cilia were significantly enriched among upregulated genes during differentiation, including genes linked to ciliopathies with neurodevelopmental phenotypes. We confirmed the presence of primary cilia throughout neuronal differentiation. Focusing on dyslexia candidate genes, 33 out of 50 DD candidate genes were detected in NES cells by RNA sequencing, and seven candidate genes were upregulated during differentiation to neurons, including DYX1C1 (DNAAF4), a highly replicated DD candidate gene. Our results suggest a role of ciliary genes in differentiating neuronal cells and show that NES cells provide a relevant human neuronal model to study ciliary and DD candidate genes.

リンク情報
DOI
https://doi.org/10.1007/s12035-020-01905-6
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/32445086
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7320047
ID情報
  • DOI : 10.1007/s12035-020-01905-6
  • PubMed ID : 32445086
  • PubMed Central 記事ID : PMC7320047

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