Neural differentiation of human embryonic stem cells induced by the transgene-mediated overexpression of single transcription factors

Misako Matsushita, Yuhki Nakatake, Itaru Arai, Keiji Ibata, Kazuhisa Kohda, Sravan K. Goparaju, Miyako Murakami, Miki Sakota, Nana Chikazawa-Nohtomi, Shigeru B.H. Ko, Takanori Kanai, Michisuke Yuzaki, Minoru S.H. Ko

研究成果: Article査読

15 被引用数 (Scopus)

抄録

Pluripotent human embryonic stem cells (hESCs) can differentiate into multiple cell lineages, thus, providing one of the best platforms to study molecular mechanisms during cell differentiation. Recently, we have reported rapid and efficient differentiation of hESCs into functional neurons by introducing a cocktail of synthetic mRNAs encoding five transcription factors (TFs): NEUROG1, NEUROG2, NEUROG3, NEUROD1, and NEUROD2. Here we further tested a possibility that even single transcription factors, when expressed ectopically, can differentiate hESCs into neurons. To this end, we established hESC lines in which each of these TFs can be overexpressed by the doxycycline-inducible piggyBac vector. The overexpression of any of these five TFs indeed caused a rapid and rather uniform differentiation of hESCs, which were identified as neurons based on their morphologies, qRT-PCR, and immunohistochemistry. Furthermore, calcium-imaging analyses and patch clamp recordings demonstrated that these differentiated cells are electrophysiologically functional. Interestingly, neural differentiations occurred despite the cell culture conditions that rather promote the maintenance of the undifferentiated state. These results indicate that over-expression of each of these five TFs can override the pluripotency-specific gene network and force hESCs to differentiate into neurons.

本文言語English
ページ(範囲)296-301
ページ数6
ジャーナルBiochemical and Biophysical Research Communications
490
2
DOI
出版ステータスPublished - 2017 8 19

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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