RRC ID 54938
Author Horie T, Horie R, Chen K, Cao C, Nakagawa M, Kusakabe TG, Satoh N, Sasakura Y, Levine M.
Title Regulatory cocktail for dopaminergic neurons in a protovertebrate identified by whole-embryo single-cell transcriptomics.
Journal Genes Dev
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.
Volume 32(19-20)
Pages 1297-1302
Published 2018-10-1
DOI 10.1101/gad.317669.118
PII gad.317669.118
PMID 30228204
PMC PMC6169837
MeSH Animals Cell Differentiation Ciona intestinalis / embryology Ciona intestinalis / genetics* Ciona intestinalis / growth & development Ciona intestinalis / metabolism Dopaminergic Neurons / cytology Dopaminergic Neurons / metabolism* Embryo, Nonmammalian / metabolism Gene Expression Profiling Gene Regulatory Networks Single-Cell Analysis Transcription Factors / metabolism
IF 8.99
Times Cited 7
C.intestinalis / (O.japonicus) Wild C. int Tg[MiCiTHK]2