title: All-optical regulation of gene expression in targeted cells.
abstract: Controllable gene expression is always a challenge and of great significance to biomedical research and clinical applications. Recently, various approaches based on extra-engineered light-sensitive proteins have been developed to provide optogenetic actuators for gene expression. Complicated biomedical techniques including exogenous genes engineering, transfection, and material delivery are needed. Here we present an all-optical method to regulate gene expression in targeted cells. Intrinsic or exogenous genes can be activated by a Ca(2+)-sensitive transcription factor nuclear factor of activated T cells (NFAT) driven by a short flash of femtosecond-laser irradiation. When applied to mesenchymal stem cells, expression of a differentiation regulator Osterix can be activated by this method to potentially induce differentiation of them. A laser-induced "Ca(2+)-comb" (LiCCo) by multi-time laser exposure is further developed to enhance gene expression efficiency. This noninvasive method hence provides an encouraging advance of gene expression regulation, with promising potential of applying in cell biology and stem-cell science.
authors.affiliation: Ultrafast Laser Laboratory, Key Laboratory of Optoelectronic Information Technology (Ministry of Education), College of Precision Instrument and Optoelectronics Engineering, Tianjin University, Tianjin, 300072, P.R. China.
authors.forename: Yisen
authors.initials: Y
authors.lastname: Wang
authors.affiliation: 1] Ultrafast Laser Laboratory, Key Laboratory of Optoelectronic Information Technology (Ministry of Education), College of Precision Instrument and Optoelectronics Engineering, Tianjin University, Tianjin, 300072, P.R. China [2] Med-X Research Institute, School of Biomedical Engineering, Shanghai Jiaotong University, Shanghai, 200030, P.R. China.
authors.forename: Hao
authors.initials: H
authors.lastname: He
authors.affiliation: 1] Key Laboratory of microbial functional genomics of Ministry of Education, College of Life Sciences, Nankai University, Tianjin, 300072, P.R. China [2].
authors.forename: Shiyang
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Endodontics, School of Stomatology, Tianjin Medical University, Tianjin, 300072, P.R. China.
authors.forename: Dayong
authors.initials: D
authors.lastname: Liu
authors.affiliation: Key Laboratory of microbial functional genomics of Ministry of Education, College of Life Sciences, Nankai University, Tianjin, 300072, P.R. China.
authors.forename: Bei
authors.initials: B
authors.lastname: Lan
authors.affiliation: Ultrafast Laser Laboratory, Key Laboratory of Optoelectronic Information Technology (Ministry of Education), College of Precision Instrument and Optoelectronics Engineering, Tianjin University, Tianjin, 300072, P.R. China.
authors.forename: Minglie
authors.initials: M
authors.lastname: Hu
authors.affiliation: Key Laboratory of microbial functional genomics of Ministry of Education, College of Life Sciences, Nankai University, Tianjin, 300072, P.R. China.
authors.forename: Youjia
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Ultrafast Laser Laboratory, Key Laboratory of Optoelectronic Information Technology (Ministry of Education), College of Precision Instrument and Optoelectronics Engineering, Tianjin University, Tianjin, 300072, P.R. China.
authors.forename: Chingyue
authors.initials: C
authors.lastname: Wang
mesh_terms: D015153:Blotting, Western; D002454:Cell Differentiation / Q000235:genetics / Q000528:radiation effects*; D002478:Cells, Cultured; D015870:Gene Expression / Q000528:radiation effects*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007834:Lasers; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000528:radiation effects*; D018613:Microscopy, Confocal; D050778:NFATC Transcription Factors / Q000235:genetics / Q000378:metabolism; D000076182:Sp7 Transcription Factor; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D050778:NFATC Transcription Factors; D000076182:Sp7 Transcription Factor; C478163:SP7 protein, human; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D049452:Green Fluorescent Proteins