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Electrophysiological characterization of photoreceptor-like cells in human inducible pluripotent stem cell-derived retinal organoids during in vitro maturation

文献类型：期刊论文

作者Li, Lingyun8,9; Zhao, Huan7; Xie, Haohuan8; Akhtar, Tasneem8; Yao, Yichuan8; Cai, Yuan9; Dong, Kai9; Gu, Yonghao9; Bao, Jin6,8; Chen, Jutao1,6,8
刊名STEM CELLS
出版日期2021-03-08
ISSN号1066-5099
关键词differentiation hiPSC ion channel patch clamp retinal organoid
DOI10.1002/stem.3363
通讯作者Zhao, Huan() ; Xu, Weiping() ; Xue, Tian(xuetian@ustc.edu.cn)
英文摘要Retinal organoids (ROs) derived from human inducible pluripotent stem cells (hiPSCs) exhibit considerable therapeutic potential. However, current quality control of ROs during in vitro differentiation is largely limited to the detection of molecular markers, often by immunostaining, polymerase chain reaction (PCR) assays and sequencing, often without proper functional assessments. As such, in the current study, we systemically characterized the physiological maturation of photoreceptor-like cells in hiPSC-derived ROs. By performing patch-clamp recordings from photoreceptor-like cells in ROs at distinct differentiation stages (ie, Differentiation Day [D]90, D150, and D200), we determined the electrophysiological properties of the plasma membrane and several characteristic ion channels closely associated with the physiological functions of the photoreceptors. Ionic hallmarks, such as hyperpolarization-activated cyclic nucleotide-gated (HCN) channels and cyclic nucleotide-gated (CNG) channels, matured progressively during differentiation. After D200 in culture, these characteristic currents closely resembled those in macaque or human native photoreceptors. Furthermore, we demonstrated that the hyperpolarization-activated inward current/depolarization-activated outward current ratio (I-120/I+40), termed as the inward-outward current (IOC) ratio hereon, accurately represented the maturity of photoreceptors and could serve as a sensitive indicator of pathological state. Thus, this study provides a comprehensive dataset describing the electrophysiological maturation of photoreceptor-like cells in hiPSC-derived ROs for precise and sensitive quality control during RO differentiation.
资助项目Anhui Provincial Key RD Program[1804h08020252] ; National Key Basic Research Program of China[2020YFA0112200] ; National Natural Science Foundation of China[31322024] ; National Natural Science Foundation of China[31571073] ; National Natural Science Foundation of China[31601134] ; National Natural Science Foundation of China[52072360] ; National Natural Science Foundation of China[61727811] ; National Natural Science Foundation of China[61890953] ; National Natural Science Foundation of China[81400407] ; National Natural Science Foundation of China[81790644] ; National Natural Science Foundation of China[81925009] ; National Natural Science Foundation of China[91432104] ; Natural Science Foundation of Anhui Province[1408085QH159] ; Natural Science Foundation of Anhui Province[1708085QC57] ; Natural Science Foundation of Anhui Province[1808085MH289] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDA16020603] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDB02010011] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDB39000000]
WOS研究方向Cell Biology ; Biotechnology & Applied Microbiology ; Oncology ; Hematology
语种英语
出版者WILEY
WOS记录号WOS:000626172800001
资助机构Anhui Provincial Key RD Program ; National Key Basic Research Program of China ; National Natural Science Foundation of China ; Natural Science Foundation of Anhui Province ; Strategic Priority Research Program of the Chinese Academy of Sciences
源URL[http://ir.hfcas.ac.cn:8080/handle/334002/120789]  
专题中国科学院合肥物质科学研究院
通讯作者Zhao, Huan; Xu, Weiping; Xue, Tian
作者单位1.Chinese Acad Sci, Ctr Excellence Brain Sci & Intelligence Technol, Shanghai, Peoples R China
2.Univ Sci & Technol China, Affiliated Hosp 1, Div Life Sci & Med, Hefei 230001, Anhui, Peoples R China
3.Anhui Prov Key Lab Tumor Immunotherapy & Nutr The, Hefei, Peoples R China
4.Key Lab Anhui Prov High Field Magnet Resonance Im, Hefei, Peoples R China
5.Chinese Acad Sci, High Field Magnet Lab, Hefei, Peoples R China
6.Univ Sci & Technol China, Hefei Natl Lab Phys Sci Microscale, Hefei, Peoples R China
7.Hefei Univ, Sch Biol Food & Environm, Hefei 230601, Anhui, Peoples R China
8.Univ Sci & Technol China, Sch Life Sci, CAS Key Lab Brain Funct & Dis, Hefei, Peoples R China
9.Univ Sci & Technol China, Affiliated Hosp 1, Div Life Sci & Med, Ctr Eye, Hefei 230001, Anhui, Peoples R China
推荐引用方式
GB/T 7714		 Li, Lingyun,Zhao, Huan,Xie, Haohuan,et al. Electrophysiological characterization of photoreceptor-like cells in human inducible pluripotent stem cell-derived retinal organoids during in vitro maturation[J]. STEM CELLS,2021.
APA Li, Lingyun.,Zhao, Huan.,Xie, Haohuan.,Akhtar, Tasneem.,Yao, Yichuan.,...&Xue, Tian.(2021).Electrophysiological characterization of photoreceptor-like cells in human inducible pluripotent stem cell-derived retinal organoids during in vitro maturation.STEM CELLS.
MLA Li, Lingyun,et al."Electrophysiological characterization of photoreceptor-like cells in human inducible pluripotent stem cell-derived retinal organoids during in vitro maturation".STEM CELLS (2021).

入库方式： OAI收割

来源：合肥物质科学研究院

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