Biology subjects

MacMillan, H. J.

Publications and source records attributed to MacMillan, H. J..

3 recordsLinked to original sources

bioRxiv2026

Translational insights into canine dorsal root ganglia cell types using cross-species comparisons

Chronic pain accounts for nearly half of owner-reported canine euthanasia decisions, yet dogs remain underutilized as a large-animal model for studying pain and developing translational therapeutics. Here, we present a canine dorsal root ganglion (DRG) cell atlas generated from six donors, representing five breeds, both sexes, and three spinal segments. Our dataset comprises 3,026 neurons and 11,734 non-neuronal cells and resolves 15 neuronal subtypes that map cleanly onto A- and C-fiber classes. We further identify eight major non-neuronal subtypes, including glial, vascular, and immune populations and characterize neuronal and non-neuronal expression of physiologically relevant neuropeptides, receptors, and ion channels. We identify region-specific differences in subtype composition between lumbar and sacral DRGs, with transcriptional programs suggestive of enhanced tactile-associated signaling in lumbar DRGs and heightened nociception-associated signaling in sacral DRGs. Cross-species comparisons reveal that canine DRG subtypes are broadly conserved with human and mouse, while also exhibiting canine-specific and canine-human shared molecular features relevant for translation. Together, this atlas serves as a valuable resource for understanding canine sensory neurobiology, comparing DRG organization across mammals, and leveraging dogs as a translational model for pain research and therapeutic development.

neuroscience↗

bioRxiv2025

A Reference Atlas of the Human Dorsal Root Ganglion

Somatosensory perception largely emerges from diverse peripheral sensory neurons whose cell bodies reside in dorsal root ganglia (DRG). Damage or dysfunction of DRG neurons is a major cause of chronic pain and sensory loss. In mice, deep single-cell transcriptomic profiling and genetically defined models have offered important clues into DRG function, but in humans, the cellular and molecular landscape of DRG neurons remains less understood. Here, we constructed a reference cell atlas of the human DRG by profiling transcriptomes of cells and nuclei from 126 donors sampled across cervical, thoracic, and lumbar DRGs. This atlas resolves 22 neuronal subtypes, including known and previously unrecognized subtypes linked to nociception, mechanosensation, thermosensation, and proprioception, as well as 10 types of non-neuronal cells. Cross-species integration, spatial transcriptomics, and microneurography enabled cell-type-specific comparisons of soma size and conduction velocity between species. Human DRG somata are larger across all cell types than their mouse counterparts, and the conduction velocities of human hair follicle innervating A-fibers are faster than in mice, suggesting a functional shift in rapid mechanical detection in humans. This integrated human DRG reference cell atlas provides a resource for exploring new molecular and physiological features of human DRG, which could help identify new strategies for treating chronic pain and other diseases of the peripheral nervous system.

neuroscience↗

bioRxiv2022

High-throughput analysis of ANRIL circRNA isoforms in human pancreatic islets

The antisense non-coding RNA in the INK locus (ANRIL) is a hotspot for genetic variants associated with cardiometabolic disease. We recently found increased ANRIL abundance in human pancreatic islets from donors with certain Type II Diabetes (T2D) risk-SNPs, including a T2D risk-SNP located within ANRIL exon 2 associated with beta cell proliferation. Recent studies have found that expression of circular species of ANRIL is linked to the regulation of cardiovascular phenotypes. Less is known about how the abundance of circular ANRIL may influence T2D phenotypes. Herein, we sequence circular RNA in pancreatic islets to characterize circular isoforms of ANRIL. We identify highly expressed circular ANRIL isoforms whose expression is correlated across dozens of individuals and characterize ANRIL splice sites that are commonly involved in back-splicing. We find that samples with the T2D risk allele in ANRIL exon 2 had higher ratios of circular to linear ANRIL compared to protective-allele carriers, and that higher circular:linear ANRIL was associated with decreased beta cell proliferation. Our study points to a combined involvement of both linear and circular ANRIL species in T2D phenotypes and opens the door for future studies of the molecular mechanisms by which ANRIL impacts cellular function in pancreatic islets.

genomics↗