bioRxivNeurosciencePreprint
Expression profiling of the mature C. elegans nervous system by single-cell RNA-Sequencing
Seth R. TayloriD, Gabriel SantpereiD, Molly B. ReillyiD, Lori GlenwinkeliD, Abigail PoffiD, Rebecca D. McWhirter, Chuan XuiD, Alexis WeinrebiD, Manasa Basavaraju, Steven J. CookiD, Alec Barrett, Alexander J. AbramsiD, Berta Vidal, Cyril CrosiD, Ibnul RafiiD, Nenad ŠestaniD, Marc HammarlundiD, Oliver HobertiD, David M. MilleriD
Abstract
A single neuron and its synapses define the fundamental structural motif of the brain but the underlying gene expression programs that specify individual neuron types are poorly understood. To address this question in a model organism, we have produced a gene expression profile of >90% of the individual neuron classes in the C. elegans nervous system, an ensemble of neurons for which both the anatomy and connectivity are uniquely defined at single cell resolution. We generated single cell transcriptomes for 52,412 neurons that resolve as clusters corresponding to 109 of the canonical 118 neuron classes in the mature hermaphrodite nervous system. Detailed analysis revealed molecular signatures that further subdivide identified classes into specific neuronal subtypes. Notably, neuropeptide-related genes are often differentially expressed between subtypes of the given neuron class which points to distinct functional characteristics. All of these data are publicly available at our website (http://www.cengen.org) and can be interrogated at the web application SCeNGEA (https://cengen.shinyapps.io/SCeNGEA). We expect that this gene expression catalog will spur the goal of delineating the underlying mechanisms that define the developmental lineage, detailed anatomy, synaptic connectivity and function of each type of C. elegans neuron.
Abstract summary
Claude Opus 5.5 · xhigh effort · 18 Oct 2026 · from the abstract · CC BY-NC-ND 4.0
Transcriptomes of 52,412 neurons resolve 109 of the 118 canonical hermaphrodite neuron classes, and neuropeptide genes separate subtypes inside individual classes.
Which gene expression programmes specify individual neuron types is largely unknown, and the C. elegans nervous system has its anatomy and connectivity defined at single-cell resolution. Profiling nearly all of its neuron classes puts expression on the same footing as that anatomy, so molecular identity can be lined up with known connectivity.
Key results
ShownSingle-cell profiling covers more than nine in ten neuron classes of the mature hermaphrodite nervous system, with clusters matching named canonical classes.
52,412 single-neuron transcriptomes resolve into clusters corresponding to 109 of the canonical 118 classes, stated as >90% of individual neuron classes; the abstract gives no per-class cell counts or cluster quality metrics. · Abstract
ClaimedExpression signatures split recognised neuron classes further into subtypes, so the canonical class list is coarser than the molecular diversity.
Reported from the clustering analysis; the abstract names no subtype, no number of subtypes and no statistical criterion for the split. · Abstract
SuggestedNeuropeptide-related genes are a recurring source of difference between subtypes of the same class, which the authors read as distinct functional properties.
Described as frequent differential expression between subtypes; no gene lists, effect sizes or functional tests accompany it in the abstract. · Abstract
Methods, data and reproducibility
Single-cell RNA sequencing of neurons from the mature C. elegans hermaphrodite nervous system, clustering the profiles and assigning clusters to canonical neuron classes, then examining within-class signatures that define subtypes.
- Single-cell transcriptomes of neurons from the mature hermaphrodite nervous system · C. elegans · n = 52,412 neurons
- Methods & tools
- SCeNGEA
- Data & accessions
- http://www.cengen.org/https://cengen.shinyapps.io/SCeNGEA
- Reproducibility gaps
- Access is through a project website and a browser application; no sequencing accession, processed count matrix or analysis code is named in the abstract.
Limitations (2)
- Coverage is incomplete: clusters correspond to 109 of the 118 canonical classes, so a handful of classes are missing and the abstract does not say which or why. · noted in this summary
- Subtypes are defined from expression alone, with no anatomical, lineage or functional confirmation reported that the proposed subdivisions are real distinctions. · noted in this summary
Read this if you need a neuron-class-resolved C. elegans expression reference, or markers to separate neuronal subtypes in a nervous system with a mapped connectome.
- Citations
- 47
Reproducibility ledger
Nobody has reported trying to reproduce this paper yet. Did you replicate an experiment or run the code? Your report saves the next lab a week.
Sign in to file a reproducibility report.
Related papers
- Molecular topography of an entire nervous system
Seth R. Taylor, Gabriel Santpere, … David M. Miller·CellPeer-reviewed·Jul 7, 2021
- Combining single-cell RNA-sequencing with a molecular atlas unveils new markers for C. elegans neuron classes.
Ramiro Lorenzo, Michiho Onizuka, … Patrick Laurent·Nucleic Acids ResearchPeer-reviewed·May 27, 2020
- Integrating bulk and single cell RNA-seq refines transcriptomic profiles of individual C. elegans neurons
Alec Barrett, Erdem Varol, … Marc Hammarlund·bioRxiv·Jan 26, 2025
- Integrating bulk and single cell RNA-seq refines transcriptomic profiles of individual C. elegans neurons
Alec Barrett, Erdem Varol, … Marc Hammarlund·bioRxiv·Apr 5, 2022
- A gene expression atlas of a juvenile nervous system
Seth R. Taylor, Claire E. Olson, … David M. Miller·bioRxiv·Nov 21, 2025
- A neurotransmitter atlas of C.elegans males and hermaphrodites
Chen Wang, Berta Vidal, … Oliver Hobert·eLifePeer-reviewed·Oct 18, 2024