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

ACS Synthetic Biology
Yuichi FuruhataKeitaro Yoshimoto

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.

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Citations

Dec 6, 2018·The Journal of Bone and Joint Surgery. American Volume·Matthew J Allen
Sep 11, 2019·Journal of Clinical Medicine·Armita Mahdavi GorabiAmirhossein Sahebkar
Dec 6, 2019·International Journal of Molecular Sciences·Sergey BrezginVladimir Chulanov
Oct 31, 2020·Nucleic Acids Research·Jing ZhaoMakoto Miyagishi
Apr 4, 2021·International Journal of Molecular Sciences·Yoojin SeoHyung-Sik Kim
Jun 21, 2021·Signal Transduction and Targeted Therapy·Chenya ZhuoMingqiang Li
Feb 6, 2020·Molecular Therapy. Methods & Clinical Development·Jaehoon ChoiNathaniel S Hwang

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