Diversity of satellite glia in sympathetic and sensory ganglia

Abstract

Satellite glia are the major glial type found in sympathetic and sensory ganglia in the peripheral nervous system, and specifically, contact neuronal cell bodies. Sympathetic and sensory neurons differ in morphological, molecular, and electrophysiological properties. However, the molecular diversity of the associated satellite glial cells remains unclear. Here, using single-cell RNA sequencing analysis, we identify five different populations of satellite glia from sympathetic and sensory ganglia. We define three shared populations of satellite glia enriched in immune-response genes, immediate-early genes, and ion channels/ECM-interactors, respectively. Sensory-and sympathetic-specific satellite glia are differentially enriched for modulators of lipid synthesis and metabolism. Sensory glia are also specifically enriched for genes involved in glutamate turnover. Furthermore, satellite glia and Schwann cells can be distinguished by unique transcriptional signatures. This study reveals the remarkable heterogeneity of satellite glia in the peripheral nervous system.

Satellite glia modulate sympathetic neuron survival, activity, and autonomic function

“…In the adult PNS, BLBP expression is restricted to satellite glia and is not detected in Schwann cells based on single-cell RNA-sequencing analysis and characterization of Fabp7-CreER2- driven reporter mice ( Avraham et al, 2020 ). Using data sets from our recently published single-cell RNA-sequencing analysis of peripheral sympathetic and sensory ganglia from adult mice (postnatal days 30–45) ( Mapps et al, 2022 ), we found that BLBP ( Fabp7 ) is ~140-fold enriched in satellite glial cells compared to other ganglionic cell types ( Figure 1—figure supplement 1A ). Of note, Schwann cells are scarce in adult sympathetic ganglia compared to sensory ganglia based on single-cell RNA-sequencing analyses ( Mapps et al, 2022 ).…”

“…Using data sets from our recently published single-cell RNA-sequencing analysis of peripheral sympathetic and sensory ganglia from adult mice (postnatal days 30–45) ( Mapps et al, 2022 ), we found that BLBP ( Fabp7 ) is ~140-fold enriched in satellite glial cells compared to other ganglionic cell types ( Figure 1—figure supplement 1A ). Of note, Schwann cells are scarce in adult sympathetic ganglia compared to sensory ganglia based on single-cell RNA-sequencing analyses ( Mapps et al, 2022 ). To further ensure the cellular specificity of BLBP, we generated genetic reporter mice by crossing Fabp7-CreER2 mice with ROSA26 mEGFP mice ( Muzumdar et al, 2007 ), which drives expression of membrane-tagged EGFP ( Figure 1—figure supplement 1B ).…”

“…Fabp7, which encodes for brain lipid binding protein (BLBP), a fatty acid transporter, is one of the most highly expressed transcripts in mouse satellite glial cells ( Avraham et al, 2020 ; Kurtz et al, 1994 ; Mapps et al, 2022 ). Using immunostaining for BLBP and tyrosine hydroxylase (TH), a marker for noradrenergic sympathetic neurons, we observed BLBP-positive satellite glia in the mouse sympathetic ganglia (superior cervical ganglia [SCG]) at both developmental and adult stages ( Figure 1A ).…”

“… ( A ) Fabp7 mRNA is enriched in satellite glial cells compared to other ganglionic cell types based on single-cell RNA-sequencing analysis of sympathetic (superior cervical ganglia) and sensory (dorsal root ganglia) from adult mice (postnatal days 30–45) ( Mapps et al, 2022 ). Expression is normalized to cell counts for individual ganglionic cell types.…”

Schwann cell precursors represent a neural crest‐like state with biased multipotency

“…Validation of tSC population using published NMJ bulk RNAseq data Published bulk RNA seq data containing nonmyelinating, synaptic glia of the neuromuscular junction (NMJ; Mapps et al, 2022) was downloaded and processed as follows: fastq files were aligned with STAR tool and count matrices generate via featureCounts using mouse genome annotation gencode M27. Count matrix was then analysed via DESeq2 pipeline, where the covariate to compare was FACS sorting of cells being S100β-GFP + or S100β-GFP + /NG2-dsRed.…”