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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Main Authors: Katherine S. Morillo, Jonathan St. Ange, Yifei Weng, Rachel Kaletsky, Coleen T. Murphy
Format: Article
Language:English
Published: Elsevier 2025-08-01
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.
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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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