Control of Adipogenic Differentiation in Mesenchymal Stem Cells via Endogenous Gene Activation Using CRISPR-Cas9

Yuichi Furuhata, Yuta Nihongaki, Moritoshi Sato, Keitaro Yoshimoto

Research output: Contribution to journalArticlepeer-review

Abstract

Mesenchymal stem cells (MSCs) are of interest in regenerative medicine owing to their multilineage differentiation and self-renewal properties. Understanding the in vivo differentiation process is necessary for clinical applications including cell therapy and transplantation. This remains challenging owing to the lack of induction methods that imitate the natural programming process. Endogenous gene regulation of tissue-specific transcription factors is therefore desirable. In the present study, we demonstrated endogenous activation of adipogenic genes through the dCas9-based transcription system and achieved efficient induction of different types of adipocyte-like cells from MSCs. Interestingly, the MSCs converted via single-gene activation exhibited morphological and molecular properties of white adipocytes, while beige adipocyte-like cells were induced via multiplex gene activation of three specific transcription factors. These results reveal that the fate of MSCs can be effectively manipulated by direct activation of specific endogenous gene expression using a dCas9-based activator with reduced exogenous additives.

Original languageEnglish (US)
Pages (from-to)2191-2197
Number of pages7
JournalACS Synthetic Biology
Volume6
Issue number12
DOIs
StatePublished - Dec 15 2017
Externally publishedYes

Keywords

  • beige adipocyte
  • CRISPR-Cas9
  • differentiation
  • gene activation
  • mesenchymal stem cells
  • white adipocyte

ASJC Scopus subject areas

  • Biomedical Engineering
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)

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