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\n\n \n \n Chacha, P. P., Horie, R., Kusakabe, T. G., Sasakura, Y., Singh, M., Horie, T., & Levine, M.\n\n\n \n \n \n \n \n Neuronal identities derived by misexpression of the POU IV sensory determinant in a protovertebrate.\n \n \n \n \n\n\n \n\n\n\n
Proceedings of the National Academy of Sciences, 119(4): e2118817119. January 2022.\n
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@article{chacha_neuronal_2022,\n\ttitle = {Neuronal identities derived by misexpression of the {POU} {IV} sensory determinant in a protovertebrate},\n\tvolume = {119},\n\turl = {http://www.pnas.org/content/119/4/e2118817119.abstract},\n\tdoi = {10.1073/pnas.2118817119},\n\tabstract = {The protovertebrate Ciona intestinalis is an ideal system to investigate both gene regulatory networks that underlie cell-type specification and how cell types have evolved. In this study, we use single-cell technology, experimental manipulations, and computational analyses to understand the role of the regulatory determinant POU IV—a homolog of Brn3 in vertebrates—in specifying various sensory cell types in Ciona. Surprisingly, the misexpression of POU IV throughout the epidermis led to the formation of hybrid sensory cell types, including those exhibiting properties of both palp sensory cells and bipolar tail neurons. These results demonstrate the interconnectedness of diverse sensory specification networks and give insights into the opportunities and challenges of reprogramming cell types through the targeted misexpression of cellular determinants.The protovertebrate Ciona intestinalis type A (sometimes called Ciona robusta) contains a series of sensory cell types distributed across the head–tail axis of swimming tadpoles. They arise from lateral regions of the neural plate that exhibit properties of vertebrate placodes and neural crest. The sensory determinant POU IV/Brn3 is known to work in concert with regional determinants, such as Foxg and Neurogenin, to produce palp sensory cells (PSCs) and bipolar tail neurons (BTNs), in head and tail regions, respectively. A combination of single-cell RNA-sequencing (scRNA-seq) assays, computational analysis, and experimental manipulations suggests that misexpression of POU IV results in variable transformations of epidermal cells into hybrid sensory cell types, including those exhibiting properties of both PSCs and BTNs. Hybrid properties are due to coexpression of Foxg and Neurogenin that is triggered by an unexpected POU IV feedback loop. Hybrid cells were also found to express a synthetic gene battery that is not coexpressed in any known cell type. We discuss these results with respect to the opportunities and challenges of reprogramming cell types through the targeted misexpression of cellular determinants.All study data are included in the article and/or SI Appendix. All code, analyses, and files can be accessed from the GitHub repository https://github.com/Singh-Lab/Pou4\\_Misexpression. In addition, the data discussed in this publication have been deposited in NCBI's Gene Expression Omnibus (Chacha et al., 2021) and are accessible through GEO Series accession number GSE192645 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE192645).},\n\tnumber = {4},\n\tjournal = {Proceedings of the National Academy of Sciences},\n\tauthor = {Chacha, Prakriti Paul and Horie, Ryoko and Kusakabe, Takehiro G. and Sasakura, Yasunori and Singh, Mona and Horie, Takeo and Levine, Michael},\n\tmonth = jan,\n\tyear = {2022},\n\tpages = {e2118817119},\n}\n\n
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\n The protovertebrate Ciona intestinalis is an ideal system to investigate both gene regulatory networks that underlie cell-type specification and how cell types have evolved. In this study, we use single-cell technology, experimental manipulations, and computational analyses to understand the role of the regulatory determinant POU IV—a homolog of Brn3 in vertebrates—in specifying various sensory cell types in Ciona. Surprisingly, the misexpression of POU IV throughout the epidermis led to the formation of hybrid sensory cell types, including those exhibiting properties of both palp sensory cells and bipolar tail neurons. These results demonstrate the interconnectedness of diverse sensory specification networks and give insights into the opportunities and challenges of reprogramming cell types through the targeted misexpression of cellular determinants.The protovertebrate Ciona intestinalis type A (sometimes called Ciona robusta) contains a series of sensory cell types distributed across the head–tail axis of swimming tadpoles. They arise from lateral regions of the neural plate that exhibit properties of vertebrate placodes and neural crest. The sensory determinant POU IV/Brn3 is known to work in concert with regional determinants, such as Foxg and Neurogenin, to produce palp sensory cells (PSCs) and bipolar tail neurons (BTNs), in head and tail regions, respectively. A combination of single-cell RNA-sequencing (scRNA-seq) assays, computational analysis, and experimental manipulations suggests that misexpression of POU IV results in variable transformations of epidermal cells into hybrid sensory cell types, including those exhibiting properties of both PSCs and BTNs. Hybrid properties are due to coexpression of Foxg and Neurogenin that is triggered by an unexpected POU IV feedback loop. Hybrid cells were also found to express a synthetic gene battery that is not coexpressed in any known cell type. We discuss these results with respect to the opportunities and challenges of reprogramming cell types through the targeted misexpression of cellular determinants.All study data are included in the article and/or SI Appendix. All code, analyses, and files can be accessed from the GitHub repository https://github.com/Singh-Lab/Pou4_Misexpression. In addition, the data discussed in this publication have been deposited in NCBI's Gene Expression Omnibus (Chacha et al., 2021) and are accessible through GEO Series accession number GSE192645 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE192645).\n
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