@article{e9f6ed81556241e2993048debe416723,
title = "Regulatory cocktail for dopaminergic neurons in a protovertebrate identified by whole-embryo single-cell transcriptomics",
abstract = "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.",
keywords = "Ascidian, Ciona CNS, Dopamine, Neuronal differentiation, Single-cell transcriptomics",
author = "Takeo Horie and Ryoko Horie and Kai Chen and Chen Cao and Masashi Nakagawa and Kusakabe, {Takehiro G.} and Noriyuki Satoh and Yasunori Sasakura and Michael Levine",
note = "Funding Information: We thank all the members of the Lewis-Sigler Institute Genome Facility for technical support of the single-cell RNA-seq assays and analysis. We also thank Reiko Yoshida, Chikako Imaizumi, and all other members of the staff at the Maizuru Fisheries Research Station of Kyoto University for providing C. intestinalis. This study was supported by a grant from the National Institutes of Health to M.L. (NS076542) and Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science to Y.S. (20681019 and 16H04815), T.H. (24687008 and 16K07433), T.G.K. (16H04724), and N.S. (20247031 and 16H04824). T.H. was supported by Pre-Strategic Research for Embryonic Science and Technology from the Japan Science and Technology Agency and by Pre-Strategic Initiatives from University of Tsukuba. Y.S. was supported by the Toray Science and Technology Grant. This study was further supported by the National Funding Information: We thank all the members of the Lewis-Sigler Institute Genome Facility for technical support of the single-cell RNA-seq assays and analysis. We also thank Reiko Yoshida, Chikako Imaizumi, and all other members of the staff at the Maizuru Fisheries Research Station of Kyoto University for providing C. intestinalis. This study was supported by a grant from the National Institutes of Health to M.L. (NS076542) and Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science to Y.S. (20681019 and 16H04815), T.H. (24687008 and 16K07433), T.G.K. (16H04724), and N.S. (20247031 and 16H04824). T.H. was supported by Pre-Strategic Research for Embryonic Science and Technology from the Japan Science and Technology Agency and by Pre-Strategic Initiatives from University of Tsukuba. Y.S. was supported by the Toray Science and Technology Grant. This study was further supported by the National Bio-Resource Project (NBRP) of the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan. Publisher Copyright: {\textcopyright} 2018 Horie et al.",
year = "2018",
doi = "10.1101/GAD.317669.118",
language = "English (US)",
volume = "32",
pages = "1297--1302",
journal = "Genes and Development",
issn = "0890-9369",
publisher = "Cold Spring Harbor Laboratory Press",
number = "19-20",
}