Single-nucleus neuronal transcriptional profiling of male C. elegans uncovers regulators of sex-specific and sex-shared behaviors
Summary: Sexual differentiation of the nervous system drives profound neurobiological and behavioral differences between the sexes across various organisms, including Caenorhabditis elegans. Using single-nucleus RNA sequencing, we profiled and compared adult male and hermaphrodite C. elegans neurons...
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| Language: | English |
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Elsevier
2025-08-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124725007879 |
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| author | Katherine S. Morillo Jonathan St. Ange Yifei Weng Rachel Kaletsky Coleen T. Murphy |
| author_facet | Katherine S. Morillo Jonathan St. Ange Yifei Weng Rachel Kaletsky Coleen T. Murphy |
| author_sort | Katherine S. Morillo |
| collection | DOAJ |
| description | Summary: Sexual differentiation of the nervous system drives profound neurobiological and behavioral differences between the sexes across various organisms, including Caenorhabditis elegans. Using single-nucleus RNA sequencing, we profiled and compared adult male and hermaphrodite C. elegans neurons, generating an atlas of adult male-specific and sex-shared neurons. We expanded the molecular map of male-specific neurons and identified highly dimorphic expression of G protein-coupled receptors (GPCRs), neuropeptides, and ion channels. Our data demonstrate sex-shared neurons exhibit substantial heterogeneity between the sexes, while sex-specific neurons repurpose conserved molecular pathways to regulate dimorphic behaviors. We show that the PHD neurons display remarkable similarity to sex-shared AWA neurons, suggesting partial repurposing of conserved pathways, and that they and the GPCR SRT-18 may play a role in pheromone sensing. We further demonstrate that the ubiquitously expressed MAPK phosphatase vhp-1 regulates both sex-specific and sex-shared behaviors. Our data provide a rich resource for discovering sex-specific transcriptomic differences and the molecular basis of sex-specific behaviors. |
| format | Article |
| id | doaj-art-8d7caa3b255c421c821cc7c779a37e2a |
| institution | DOAJ |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-8d7caa3b255c421c821cc7c779a37e2a2025-08-20T03:12:57ZengElsevierCell Reports2211-12472025-08-0144811601610.1016/j.celrep.2025.116016Single-nucleus neuronal transcriptional profiling of male C. elegans uncovers regulators of sex-specific and sex-shared behaviorsKatherine S. Morillo0Jonathan St. Ange1Yifei Weng2Rachel Kaletsky3Coleen T. Murphy4Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA; LSI Genomics, Princeton University, Princeton, NJ 08544, USADepartment of Molecular Biology, Princeton University, Princeton, NJ 08544, USA; LSI Genomics, Princeton University, Princeton, NJ 08544, USADepartment of Molecular Biology, Princeton University, Princeton, NJ 08544, USA; LSI Genomics, Princeton University, Princeton, NJ 08544, USADepartment of Molecular Biology, Princeton University, Princeton, NJ 08544, USA; LSI Genomics, Princeton University, Princeton, NJ 08544, USADepartment of Molecular Biology, Princeton University, Princeton, NJ 08544, USA; LSI Genomics, Princeton University, Princeton, NJ 08544, USA; Corresponding authorSummary: Sexual differentiation of the nervous system drives profound neurobiological and behavioral differences between the sexes across various organisms, including Caenorhabditis elegans. Using single-nucleus RNA sequencing, we profiled and compared adult male and hermaphrodite C. elegans neurons, generating an atlas of adult male-specific and sex-shared neurons. We expanded the molecular map of male-specific neurons and identified highly dimorphic expression of G protein-coupled receptors (GPCRs), neuropeptides, and ion channels. Our data demonstrate sex-shared neurons exhibit substantial heterogeneity between the sexes, while sex-specific neurons repurpose conserved molecular pathways to regulate dimorphic behaviors. We show that the PHD neurons display remarkable similarity to sex-shared AWA neurons, suggesting partial repurposing of conserved pathways, and that they and the GPCR SRT-18 may play a role in pheromone sensing. We further demonstrate that the ubiquitously expressed MAPK phosphatase vhp-1 regulates both sex-specific and sex-shared behaviors. Our data provide a rich resource for discovering sex-specific transcriptomic differences and the molecular basis of sex-specific behaviors.http://www.sciencedirect.com/science/article/pii/S2211124725007879CP: GenomicsCP: Neuroscience |
| spellingShingle | Katherine S. Morillo Jonathan St. Ange Yifei Weng Rachel Kaletsky Coleen T. Murphy Single-nucleus neuronal transcriptional profiling of male C. elegans uncovers regulators of sex-specific and sex-shared behaviors Cell Reports CP: Genomics CP: Neuroscience |
| title | Single-nucleus neuronal transcriptional profiling of male C. elegans uncovers regulators of sex-specific and sex-shared behaviors |
| title_full | Single-nucleus neuronal transcriptional profiling of male C. elegans uncovers regulators of sex-specific and sex-shared behaviors |
| title_fullStr | Single-nucleus neuronal transcriptional profiling of male C. elegans uncovers regulators of sex-specific and sex-shared behaviors |
| title_full_unstemmed | Single-nucleus neuronal transcriptional profiling of male C. elegans uncovers regulators of sex-specific and sex-shared behaviors |
| title_short | Single-nucleus neuronal transcriptional profiling of male C. elegans uncovers regulators of sex-specific and sex-shared behaviors |
| title_sort | single nucleus neuronal transcriptional profiling of male c elegans uncovers regulators of sex specific and sex shared behaviors |
| topic | CP: Genomics CP: Neuroscience |
| url | http://www.sciencedirect.com/science/article/pii/S2211124725007879 |
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