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Haberberger, R. V.

Publications and source records attributed to Haberberger, R. V..

3 recordsLinked to original sources

T-cell distribution in the dorsal root ganglion across species, sex, and age

T-cells infiltrate somatosensory ganglia in response to nerve damage, autoimmune disease, and infection, contributing to sensory abnormalities and pain. In naive states, T-cells are rare in the rodent dorsal root ganglion (DRG) but have been reported in human and non-human primates without known relevant exposures. It remains unclear whether there are inherent evolutionary or species differences in DRG T-cell residence. Using a comparative biology approach, we investigated the frequency and distribution of T-cells in the mammalian DRG across humans, non-human primates, pigs, and rodents, and in humans investigated the contributions of sex and age. Spatial transcriptomics and immunofluorescence independently verified the robust presence of DRG T-cells at similar levels in humans, non-human primates, and pigs, but were fewer in rats and largely absent in mice. In humans, premenopausal females were more likely to have elevated DRG endoneurial T-cells than post-menopausal females or adult males. T-cells were detected in human dorsal root ganglion at as early as two months of age but were less abundant within the perineuronal niche. Most human DRG T-cells expressed distinct markers consistent with a resident memory (Trm) phenotype. We discuss the importance of studying the functional roles of DRG-resident T-cells and raise broader considerations for modelling peripheral nervous system disease.

neuroscience↗

Transcriptomic and histological characterization of telocytes in the human dorsal root ganglion

Telocytes are interstitial cells with long processes that cover distances in tissues and likely coordinate interacts with other cell types. Though present in central and peripheral neuronal tissues, their role remains unclear. Dorsal root ganglia (DRG) house pseudounipolar afferent neurons responsible for signals such as temperature, proprioception and nociception. This study aimed to investigate the presence and function of telocytes in human DRG by investigating their transcriptional profile, location and ultrastructure. Sequencing data revealed CD34 and PDGFRA expressing cells comprise roughly 1.5-3% of DRG cells. Combined expression of CD34 and PDGFRA is a putative marker gene set for telocytes. Further analysis identified nine subclusters with enriched cluster-specific genes. KEGG and GO pathway analysis suggested vascular, immune and connective tissue associated putative telocyte subtypes. Over 3000 potential receptor-ligand interactions between sensory neurons and these CD34 and PDGFRA expressing putative telocytes were identified using a ligand-receptors interactome platform. Immunohisto-chemistry showed CD34+ telocytes in the endoneural space of DRGs, next to neuron-satellite complexes, in perivascular spaces and in the endoneural space between nerve fibre bundles, consistent with pathway analysis. Transmission electron microscopy (TEM) confirmed their location identifying characteristic elongated nucleus, long and thin telopods containing vesicles, surrounded by a basal lamina. This is the first study that provides gene expression analysis of telocytes in complex human tissue such as the DRG, highlighting functional differences based on tissue location with no significant ultrastructural variation. Key pointsO_LIuman DRGs contain CD34/PDGFRA+ putative telocytes that can be subgrouped in nine clusters based on gene expression C_LIO_LIThe DRGs contain CD34+ telocytes in close proximity to neuron-satellite complexes, blood vessels and nerve fibre bundles. C_LIO_LIThe basic features of telocytes with elongated nuclei and thin telopods do not differ between locations. C_LI

neuroscience↗

Nageotte nodules in human DRG reveal neurodegeneration in painful diabetic neuropathy

Diabetic neuropathy is frequently accompanied by pain and loss of sensation attributed to axonal dieback. We recovered dorsal root ganglia (DRGs) from 90 organ donors, 19 of whom had medical indices for diabetic painful neuropathy (DPN). Nageotte nodules, dead sensory neurons engulfed by non-neuronal cells, were abundant in DPN DRGs and accounted for 25% of all neurons. Peripherin-and Nav1.7-positive dystrophic axons invaded Nageotte nodules, forming small neuroma-like structures. Using histology and spatial sequencing, we demonstrate that Nageotte nodules are mainly composed of satellite glia and non-myelinating Schwann cells that express SPP1 and are intertwined with sprouting sensory axons originating from neighboring neurons. Our findings solve a 100-year mystery of the nature of Nageotte nodules linking these pathological structures to pain and sensory loss in DPN.

neuroscience↗