Novel culture system via wirelessly controllable optical stimulation of the FGF signaling pathway for human and pig pluripotency

  • Choi, In Young; 
  • Lim, HoTae; 
  • Huynh, Alex; 
  • Schofield, James; 
  • Cho, Hyeon Jin; 
  • ... Oh, Yohan; 
  • 외 8명
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초록

Stem cell fate is largely determined by cellular signaling networks and is heavily dependent on the supplementation of exogenous recombinant proteins into culture media; however, uneven distribution and inconsistent stability of recombinant proteins are closely associated with the spontaneous differentiation of pluripotent stem cells (PSCs) and result in significant costs in large-scale manufacturing. Here, we report a novel PSC culture system via wirelessly controllable optical activation of the fibroblast growth factor (FGF) signaling pathway without the need for supplementation of recombinant FGF2 protein, a key molecule for maintaining pluripotency of PSCs. Using a fusion protein between the cytoplasmic region of the FGF receptor-1 and a light-oxygen-voltage domain, we achieved tunable, blue light-dependent activation of FGF signaling in human and porcine PSCs. Our data demonstrate that a highly controllable optical stimulation of the FGF signaling pathway is sufficient for long-term maintenance of PSCs, without the loss of differentiation potential into three germ layers. This culture system will be a cost-effective platform for a large-scale stem cell culture.

키워드

Optogenetics; FGF2; FGF signaling; Pluripotent stem cell; Pluripotency; Cell culture; Cell proliferation; Cell signaling; Cellular manufacturing; Chemical activation; Cost effectiveness; Mammals; Recombinant proteins; Stem cells; fibroblast growth factor receptor 1; fusion protein; Cellular signaling networks; Cytoplasmic regions; Fibroblast growth factor; Large-scale manufacturing; Light oxygen voltages; Long-term maintenances; Optical stimulation; Pluripotent stem cells; Article; cell culture; cell differentiation; cell proliferation; cost effectiveness analysis; cytoplasm; down regulation; FGF signaling; gene expression regulation; germ layer; illumination; pluripotent stem cell; priority journal; process optimization; protein domain; signal transduction; upregulation; validation process; animal; cell culture technique; embryonic stem cell; human; pig; signal transduction; Signaling
제목
Novel culture system via wirelessly controllable optical stimulation of the FGF signaling pathway for human and pig pluripotency
저자
Choi, In Young; Lim, HoTae; Huynh, Alex; Schofield, James; Cho, Hyeon Jin; Lee, Hosuk; Andersen, Peter; Shin, Joo Heon; Heo, Won Do; Hyun, Sang-Hwan; Kim, Yong Jun; Oh, Yohan; Kim, Hyesoo; Lee, Gabsang
DOI
10.1016/j.biomaterials.2020.120222
발행일
2021-02
유형
Article
저널명
Biomaterials
권
269
페이지
1 ~ 11