國家衛生研究院 NHRI:Item 3990099045/7992
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    题名: Signaling adaptor protein SH2B1 enhances neurite outgrowth and accelerates the maturation of human induced neurons
    作者: Hsu, YC;Chen, SL;Wang, YJ;Chen, YH;Wang, DY;Chen, L;Chen, CH;Chen, HH;Chiu, IM
    贡献者: Institute of Cellular and Systems Medicine;Center for Neuropsychiatric Research
    摘要: Recent advances in somatic cell reprogramming have highlighted the plasticity of the somatic epigenome, particularly through demonstrations of direct lineage reprogramming of adult mouse and human fibroblasts to induced pluripotent stem cells (iPSCs) and induced neurons (iNs) under defined conditions. However, human cells appear to be less plastic and have a higher epigenetic hurdle for reprogramming to both iPSCs and iNs. Here, we show that SH2B adaptor protein 1beta (SH2B1) can enhance neurite outgrowth of iNs reprogrammed from human fibroblasts as early as day 14, when combined with miR124 and transcription factors BRN2 and MYT1L (IBM) under defined conditions. These SH2B1-enhanced iNs (S-IBM) showed canonical neuronal morphology, and expressed multiple neuronal markers, such as TuJ1, NeuN, and synapsin, and functional proteins for neurotransmitter release, such as GABA, vGluT2, and tyrosine hydroxylase. Importantly, SH2B1 accelerated mature process of functional neurons and exhibited action potentials as early as day 14; without SH2B1, the IBM iNs do not exhibit action potentials until day 21. Our data demonstrate that SH2B1 can enhance neurite outgrowth and accelerate the maturation of human iNs under defined conditions. This approach will facilitate the application of iNs in regenerative medicine and in vitro disease modeling.
    日期: 2014-06
    關聯: Stem Cells Translational Medicine. 2014 Jun;3(6):713-722.
    Link to: http://dx.doi.org/10.5966/sctm.2013-0111
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=2157-6564&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000336940000017
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84901810076
    显示于类别:[邱英明] 期刊論文
    [陳慧諴] 期刊論文
    [陳嘉祥(2009-2013)] 期刊論文

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