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

OptogeneticsFGF2FGF signalingPluripotent stem cellPluripotencyCell cultureCell proliferationCell signalingCellular manufacturingChemical activationCost effectivenessMammalsRecombinant proteinsStem cellsfibroblast growth factor receptor 1fusion proteinCellular signaling networksCytoplasmic regionsFibroblast growth factorLarge-scale manufacturingLight oxygen voltagesLong-term maintenancesOptical stimulationPluripotent stem cellsArticlecell culturecell differentiationcell proliferationcost effectiveness analysiscytoplasmdown regulationFGF signalinggene expression regulationgerm layerilluminationpluripotent stem cellpriority journalprocess optimizationprotein domainsignal transductionupregulationvalidation processanimalcell culture techniqueembryonic stem cellhumanpigsignal transductionSignaling
제목
Novel culture system via wirelessly controllable optical stimulation of the FGF signaling pathway for human and pig pluripotency
저자
Choi, In YoungLim, HoTaeHuynh, AlexSchofield, JamesCho, Hyeon JinLee, HosukAndersen, PeterShin, Joo HeonHeo, Won DoHyun, Sang-HwanKim, Yong JunOh, YohanKim, HyesooLee, Gabsang
DOI
10.1016/j.biomaterials.2020.120222
발행일
2021-02
유형
Article
저널명
Biomaterials
269
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