Molecular heterogeneity of C. elegans glia across sexes

Abstract

A comprehensive description of nervous system function, and sex dimorphism within, is incomplete without clear assessment of the diversity of its component cell types, neurons and glia. C. elegans has an invariant nervous system with the first mapped connectome of a multi-cellular organism and single-cell atlas of component neurons. Here we present single nuclear RNA-seq evaluation of glia across the entire adult C. elegans nervous system, including both sexes. Machine learning models enabled us to identify both sex-shared and sex-specific glia and glial subclasses. We have identified and validated molecular markers in silico and in vivo for these molecular subcategories. Comparative analytics also reveals previously unappreciated molecular heterogeneity in anatomically identical glia between and within sexes, indicating consequent functional heterogeneity. Furthermore, our datasets reveal that while adult C. elegans glia express neuropeptide genes, they lack the canonical unc-31/CAPS-dependent dense core vesicle release machinery. Thus, glia employ alternate neuromodulator processing mechanisms. Overall, this molecular atlas, available at www.wormglia.org, reveals rich insights into heterogeneity and sex dimorphism in glia across the entire nervous system of an adult animal

Neuron cilia restrain glial KCC-3 to a microdomain to regulate multisensory processing

“…KCC-3 expresses in many sheath glia. 36 , 37 Cell-specific expression of KCC-3:mScarlet in two other glia, CEPsh (in the animal head) and PHsh (in the animal tail) glia, showed restricted localization of KCC-3 to anterior process ends around neuron contact sites ( Figures 3I and 3J″ ), similar to AMsh. Thus, localization of KCC-3 to anterior microdomains is a general property across C. elegans glia.…”

A neurotransmitter atlas ofC. elegansmales and hermaphrodites

“…We were not able to detect AMsh with anti-GABA staining, nor with reporter alleles of unc-25/GAD . However, since very low levels of unc-25 are observed in AMsh scRNA datasets ( Taylor et al 2021 ; Purice et al 2023 ), the abundance of GABA in AMsh may lie below conventional detection levels.…”

“…We were not able to detect AMsh with anti-GABA staining, nor with reporter alleles of unc-25/GAD. However, since very low levels of unc-25 are observed in AMsh scRNA datasets (TAYLOR et al 2021;PURICE et al 2023), the usage of GABA by AMsh does warrant further investigation. Outside the nervous system, the most prominent and functionally best characterized usage of neurotransmitters lies in the hermaphrodite somatic gonad, which has been shown to synthesize octopamine and use it to control oocyte quiescence (ALKEMA et al 2005;KIM et al 2021).…”