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Regulatory cocktail for dopaminergic neurons in a protovertebrate identified by whole-embryo single-cell transcriptomics

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-speci...

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Autores principales: Horie, Takeo, Horie, Ryoko, Chen, Kai, Cao, Chen, Nakagawa, Masashi, Kusakabe, Takehiro G., Satoh, Noriyuki, Sasakura, Yasunori, Levine, Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6169837/
https://www.ncbi.nlm.nih.gov/pubmed/30228204
http://dx.doi.org/10.1101/gad.317669.118
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author Horie, Takeo
Horie, Ryoko
Chen, Kai
Cao, Chen
Nakagawa, Masashi
Kusakabe, Takehiro G.
Satoh, Noriyuki
Sasakura, Yasunori
Levine, Michael
author_facet Horie, Takeo
Horie, Ryoko
Chen, Kai
Cao, Chen
Nakagawa, Masashi
Kusakabe, Takehiro G.
Satoh, Noriyuki
Sasakura, Yasunori
Levine, Michael
author_sort Horie, Takeo
collection PubMed
description 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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spelling pubmed-61698372019-04-01 Regulatory cocktail for dopaminergic neurons in a protovertebrate identified by whole-embryo single-cell transcriptomics Horie, Takeo Horie, Ryoko Chen, Kai Cao, Chen Nakagawa, Masashi Kusakabe, Takehiro G. Satoh, Noriyuki Sasakura, Yasunori Levine, Michael Genes Dev Research Communication 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. Cold Spring Harbor Laboratory Press 2018-10-01 /pmc/articles/PMC6169837/ /pubmed/30228204 http://dx.doi.org/10.1101/gad.317669.118 Text en © 2018 Horie et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Research Communication
Horie, Takeo
Horie, Ryoko
Chen, Kai
Cao, Chen
Nakagawa, Masashi
Kusakabe, Takehiro G.
Satoh, Noriyuki
Sasakura, Yasunori
Levine, Michael
Regulatory cocktail for dopaminergic neurons in a protovertebrate identified by whole-embryo single-cell transcriptomics
title Regulatory cocktail for dopaminergic neurons in a protovertebrate identified by whole-embryo single-cell transcriptomics
title_full Regulatory cocktail for dopaminergic neurons in a protovertebrate identified by whole-embryo single-cell transcriptomics
title_fullStr Regulatory cocktail for dopaminergic neurons in a protovertebrate identified by whole-embryo single-cell transcriptomics
title_full_unstemmed Regulatory cocktail for dopaminergic neurons in a protovertebrate identified by whole-embryo single-cell transcriptomics
title_short Regulatory cocktail for dopaminergic neurons in a protovertebrate identified by whole-embryo single-cell transcriptomics
title_sort regulatory cocktail for dopaminergic neurons in a protovertebrate identified by whole-embryo single-cell transcriptomics
topic Research Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6169837/
https://www.ncbi.nlm.nih.gov/pubmed/30228204
http://dx.doi.org/10.1101/gad.317669.118
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