Biology subjects

Boyd, J. R.

Publications and source records attributed to Boyd, J. R..

4 recordsLinked to original sources

bioRxiv2026

Intranasal HSV 1 Infection Drives Region Specific Interferon Dominant Microglial Remodeling

Background and ObjectivesHerpes simplex virus type 1 (HSV-1) is a neurotropic pathogen capable of invading the central nervous system (CNS) and increasingly associated with chronic neuroinflammation, cognitive impairment, and neurodegenerative disease. While microglia orchestrate the initial immune response to HSV-1, the molecular mechanisms that regulate their sustained neuroinflammatory activity in vivo remain poorly understood. MethodsTo define the transcriptional and epigenetic mechanisms that shape microglial responses during acute HSV-1 infection in vivo, we have, for the first time, integrated single-nucleus RNA sequencing, chromatin accessibility profiling, and spatial transcriptomics in a physiologically relevant intranasal HSV-1 infection model. ResultsSingle-cell multiome analysis of CD11b nuclei identified transcriptionally and epigenetically distinct microglial and macrophage populations. HSV-1 infection redistributed monocyte-lineage states, with a marked overrepresentation of interferon (IFN)-responsive microglia and macrophage-associated populations. These states exhibited amplification of STAT1/2-, IRF1-, and CEBPB-centered regulons, distinguishing IFN-responsive microglia from macrophage-enriched populations rather than reflecting uniform activation. Homeostatic microglial gene signatures (e.g., ApoE, Cst3) were reduced in response to HSV-1 infection. Spatial transcriptomics localized HSV-1 antigen to discrete brainstem regions, which were enriched for predicted STAT-, IRF-, and CEBPB-regulated targets identified through single-nuclei analysis. DiscussionUsing a multiomic framework, we demonstrate that HSV-1 infection drives transcriptional and epigenetic remodeling of microglial populations, characterized by a dominance of IFN-responsive states and a loss of homeostatic signatures. These findings provide mechanistic insight into how localized viral infection can reprogram microglial regulatory landscapes to maintain persistent HSV-1-associated neuroinflammation, contributing to long-term neurological vulnerability and neurodegenerative disease risk.

neuroscience↗

bioRxiv2025

Single-nuclei multiome ATAC and RNA sequencing reveals the molecular basis of thermal plasticity in Drosophila melanogaster embryos

Embryogenesis is remarkably robust to temperature variability, yet the homeostatic mechanisms that offset thermal effects during early development remain poorly understood. We measured how acclimation shifts the upper thermal limit and profiled chromatin accessibility and gene expression in D. melanogaster embryos using single-nucleus multiome sequencing. Acclimation preserved shared primordial cell types yet rapidly shifted heat tolerance. Cool-acclimated embryos showed a homeostatic response characterized by increased accessibility at binding motifs for the transcriptional activator Zelda, along with enhanced activity of gene regulatory networks in a subset of primordial cell types including the gut, muscle, and nervous system. Cool-acclimated embryos also had higher expression of ribosomal and oxidative phosphorylation genes, reflecting a coordinated increase in translation and energy production to buffer slower biochemical kinetics in the cold. Our results indicate that maintaining developmental robustness across temperature requires homeostatic gene expression responses that may carry metabolic costs constraining upper thermal limits.

developmental biology↗

bioRxiv2021

Thyroid Hormone Dependent Transcriptional Programming by TRβ Requires SWI/SNF Chromatin Remodelers

Transcriptional regulation in response to thyroid hormone (T3) is a dynamic and cell-type specific process that maintains cellular homeostasis and identity in all tissues. However, our understanding of the mechanisms of thyroid hormone receptor (TR) actions at the molecular level are actively being refined. We used an integrated genomics approach to profile and characterize the cistrome of TR{beta}, map changes in chromatin accessibility, and capture the transcriptomic changes in response to T3 in normal thyroid cells. There are significant shifts in TR{beta} genomic occupancy in response to T3, which are associated with differential chromatin accessibility, and differential recruitment of SWI/SNF chromatin remodelers. We further demonstrate selective recruitment of BAF and PBAF SWI/SNF complexes to TR{beta} binding sites, revealing novel differential functions in regulating chromatin accessibility and gene expression. Our findings highlight three distinct modes of TR{beta} interaction with chromatin and coordination of coregulator activity.

genomics↗

bioRxiv2019

Mitotic gene bookmarking by RUNX1 contributes to stabilization of the normal mammary epithelial phenotype

RUNX1 has recently been shown to play an important role in determination of mammary epithelial cell identity. However, mechanisms by which loss of the RUNX1 transcription factor in mammary epithelial cells leads to epithelial-to-mesenchymal transition (EMT) are not known. Here, we report mitotic bookmarking of genes by RUNX1 as a potential mechanism to convey regulatory information through successive cell divisions for coordinate control of mammary cell proliferation, growth, and identity. Genome-wide RUNX1 occupancy profiles for asynchronous, mitotically enriched, and early G1 breast epithelial cells reveal RUNX1 is retained during the mitosis to G1 transition on protein coding and long non-coding RNA genes critical for mammary epithelial proliferation, growth, and phenotype maintenance. Disruption of RUNX1 DNA binding and association with mitotic chromosomes alters cell morphology, global protein synthesis, and phenotype-related gene expression. Together, these findings show for the first time that RUNX1 bookmarks a subset of epithelial-related genes during mitosis that remain occupied as cells enter the next cell cycle. Compromising RUNX1 DNA binding initiates EMT, an essential first step in the onset of breast cancer. SignificanceThis study elucidates mitotic gene bookmarking as a potential epigenetic mechanism that impacts breast epithelial cell growth and phenotype and has potential implications in breast cancer onset.

cancer biology↗