Regulatory cocktail for dopaminergic neurons in a protovertebrate identified by whole-embryo single-cell transcriptomics.
Regulatory cocktail for dopaminergic neurons in a protovertebrate identified by whole-embryo single-cell transcriptomics.
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DOI：
10.1101/gad.317669.118
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发表时间：
2018-10-01
影响因子：
10.5
通讯作者：
Levine M
中科院分区：
文献类型：
--
作者：
Horie T;Horie R;Chen K;Cao C;Nakagawa M;Kusakabe TG;Satoh N;Sasakura Y;Levine M
在这项研究中，Horie等人。使用全胚胎单细胞RNA-SEQ分析来确定负责指定Ciona蝌蚪中枢神经系统中多巴胺能神经元的调控决定因素。他们的发现表明，重复使用功能操纵和单细胞RNA-SEQ分析是识别特定细胞身份规范背后的调节鸡尾酒的有效手段。原生脊椎动物的中枢神经系统包含一簇多巴胺(DA)能神经元，即冠状细胞，它们被比作脊椎动物的下丘脑。全胚胎单细胞RNA测序分析表明，Ptf1a是DA/Coronet细胞中表达最强的细胞特异性转录因子(Tf)。Ptf1a活性的下调导致它们的丢失，而错误的表达导致额外的DA/Coronet细胞的出现。光感受器细胞和室管膜细胞是最容易转化的细胞，这两种细胞都表达高水平的MEI。Ptf1a和MEI的共同表达导致了整个CNS向DA/Coronet细胞的大规模转化。因此，我们认为重复使用功能操纵和单细胞RNA-SEQ分析是识别特定细胞身份规范基础上的调节鸡尾酒的有效手段。
In this study, Horie et al. used whole-embryo single-cell RNA-seq assays to identify the regulatory determinants responsible for the specification of dopaminergic neurons in the CNS of the Ciona tadpole. Their findings suggest that the reiterative use of functional manipulations and single-cell RNA-seq assays is an effective means for the identification of regulatory cocktails underlying the specification of specific cell identities. The CNS of the protovertebrate Ciona intestinalis contains a single cluster of dopaminergic (DA) neurons, the coronet cells, which have been likened to the hypothalamus of vertebrates. Whole-embryo single-cell RNA sequencing (RNA-seq) assays identified Ptf1a as the most strongly expressed cell-specific transcription factor (TF) in DA/coronet cells. Knockdown of Ptf1a activity results in their loss, while misexpression results in the appearance of supernumerary DA/coronet cells. Photoreceptor cells and ependymal cells are the most susceptible to transformation, and both cell types express high levels of Meis. Coexpression of both Ptf1a and Meis caused the wholesale transformation of the entire CNS into DA/coronet cells. We therefore suggest that the reiterative use of functional manipulations and single-cell RNA-seq assays is an effective means for the identification of regulatory cocktails underlying the specification of specific cell identities.
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预测标记指导分化以改善基于hESC的帕金森氏病疗法的临床翻译中的移植结果。
影响因子：
23.9
作者：
Kirkeby A;Nolbrant S;Tiklova K;Heuer A;Kee N;Cardoso T;Ottosson DR;Lelos MJ;Rifes P;Dunnett SB;Grealish S;Perlmann T;Parmar M
通讯作者：
Parmar M
DOI：
10.1530/joe-15-0213
发表时间：
2015-08
期刊：
The Journal of endocrinology
影响因子：
--
作者：
Grattan DR
通讯作者：
Grattan DR
影响因子：
2.7
作者：
Moret, F;Christiaen, L;Joly, JS
通讯作者：
Joly, JS
影响因子：
2.7
作者：
Kusakabe, T;Yoshida, R;Satou, Y
通讯作者：
Satou, Y
影响因子：
16.2
作者：
Hoshino, M;Nakamura, S;Nabeshima, YI
通讯作者：
Nabeshima, YI