Biology subjects

Wood, T. A.

Publications and source records attributed to Wood, T. A..

6 recordsLinked to original sources

bioRxiv2026

Aging disrupts transcriptional programs for memory updating in the dorsal hippocampus and reveals a required role for Tent5a in reconsolidation

Existing memories can be updated with new information through a process known as reconsolidation, though the molecular mechanisms underlying this process are poorly understood. Additionally, memory updating is impaired with aging, but little is known about how this impairment occurs. Here, we used a hippocampus-dependent memory updating task alongside transcriptomics to identify which genes are upregulated in the dorsal hippocampus specifically during a memory update in both young adult mice, which show successful memory updating, and in old mice, which do not. In young mice, we observed that distinct transcriptional programs were activated by reconsolidation-dependent memory updating and memory retrieval without new information. In old mice, similar transcriptional programs were engaged by both memory updating and memory retrieval. From our sequencing results, we identified Tent5a as a novel regulator of reconsolidation-mediated memory updating, and we demonstrate that hippocampal expression of Tent5a is necessary for this process. Together, these results expand our understanding of both the underlying transcriptional mechanisms of memory updating and how these mechanisms go awry in the aged brain.

neuroscience↗

bioRxiv2026

Old mice fail to integrate a memory update into an existing hippocampal engram.

Existing memories can be updated by the presentation of new information during memory retrieval. Memory updating is impaired with age, and recent reports indicate this process is more susceptible to age-related impairments than the formation of new memories. However, the neuronal mechanisms underlying age-related updating impairments are unknown. Here, we investigated how memory engrams within the dorsal hippocampus encode a memory update in the young and old brain. We found that old mice tended to re-engage a smaller proportion of the original memory engram during the update session and chemogenetically increasing the activation of this engram alleviated age-related updating deficits. A range of therapeutically relevant behavioral and pharmacological approaches promoting re-engagement of the training engram also improved memory updating in old mice. Together, these results identify a novel mechanism by which memory updating is impaired with age and expand our understanding of how the brain organizes related information.

neuroscience↗

bioRxiv2025

Identification of QTLs linked to partial resistance to foot and root rot caused by Fusarium avenaceum and Fusarium oxysporum in faba bean (Vicia faba)

Foot and root rot, caused by a complex of soil-borne fungal and oomycete pathogens, including several Fusarium spp., can cause serious yield losses in faba bean. Current control strategies rely largely on agronomic practices and limited varietal resistance. Identifying novel sources of genetic resistance is of great potential value for breeding elite varieties with improved foot rot resistance. A partially resistant Vicia faba accession ig124213 (NV490) was crossed with a moderately susceptible ig124301 (NV512) and a mapping population comprising 198 F3 families was developed. This was screened for resistance to a mixture of seven UK field isolates of Fusarium avenaceum and Fusarium oxysporum under glasshouse conditions. Several F3 families with moderate to high levels of resistance to both Fusarium species were identified, and a high-density linkage map of the V. faba genome including 6755 SNP-markers in seven linkage groups (LG) was generated using the Vfaba_v2 Axiom SNP array. Quantitative trait loci associated with improved resistance to Fusarium foot and root rot were identified, including one major QTL on LG4, corresponding to the chromosome 4 of V. faba. Key messageThe first QTL associated with partial resistance to Fusarium foot and root rot has been identified using a biparental mapping population of Vicia faba.

plant biology↗

bioRxiv2024

Single-cell epigenomic dysregulation of Systemic Sclerosis fibroblasts via CREB1/EGR1 axis in self-assembled human skin equivalents

Systemic sclerosis (SSc) is an autoimmune disease characterized by skin fibrosis, internal organ involvement and vascular dropout. We previously developed and phenotypically characterized an in vitro 3D skin-like tissue model of SSc, and now analyze the transcriptomic (scRNA-seq) and epigenetic (scATAC-seq) characteristics of this model at single-cell resolution. SSc 3D skin-like tissues were fabricated using autologous fibroblasts, macrophages, and plasma from SSc patients or healthy control (HC) donors. SSc tissues displayed increased dermal thickness and contractility, as well as increased -SMA staining. Single-cell transcriptomic and epigenomic analyses identified keratinocytes, macrophages, and five populations of fibroblasts (labeled FB1 - 5). Notably, FB1 APOE-expressing fibroblasts were 12-fold enriched in SSc tissues and were characterized by high EGR1 motif accessibility. Pseudotime analysis suggests that FB1 fibroblasts differentiate from a TGF-{beta}1-responsive fibroblast population and ligand-receptor analysis indicates that the FB1 fibroblasts are active in macrophage crosstalk via soluble ligands including FGF2 and APP. These findings provide characterization of the 3D skin-like model at single cell resolution and establish that it recapitulates subsets of fibroblasts and macrophage phenotypes observed in skin biopsies.

genomics↗

bioRxiv2020

L-bodies are novel RNA-protein condensates driving RNA transport in Xenopus oocytes

RNP granules are membrane-less compartments within cells, formed by phase separation, that function as regulatory hubs for diverse biological processes. However, the mechanisms by which RNAs and proteins interact to promote RNP granule structure and function in vivo remain unclear. In Xenopus laevis oocytes, maternal mRNAs are transported as large RNPs to the vegetal hemisphere of the developing oocyte, where local translation is critical for proper embryonic patterning. Here, we demonstrate that vegetal transport RNPs represent a new class of cytoplasmic RNP granule, termed Localization-bodies (L-bodies). We show that L-bodies are multiphase RNP granules, containing a dynamic protein-containing phase surrounding a non-dynamic RNA-containing substructure. Our results support a role for RNA as a critical scaffold component within these RNP granules and suggest that cis-elements within localized mRNAs may drive subcellular RNA localization through control over phase behavior.

cell biology↗

bioRxiv2017

Machine Learning of the Cardiac Phenome and Skin Transcriptome to Categorize Heart Disease in Systemic Sclerosis

BackgroundCardiac involvement is a leading cause of death in systemic sclerosis (SSc/scleroderma). The complexity of SSc cardiac manifestations is not fully captured by the current clinical SSc classification, which is based on extent of skin involvement and specific autoantibodies. Therefore, we sought to develop a clinically relevant SSc cardiac disease classification to improve clinical care and increase understanding of SSc cardiac disease pathobiology. We hypothesized that machine learning could identify novel SSc cardiac disease subgroups, and that gene expression assessment of skin could provide insights into molecular pathogenesis of these SSc pheno-groups.\n\nMethodsWe used unsupervised model-based clustering (phenomapping) of SSc patient echocardiographic and clinical data to identify clinically relevant SSc pheno-groups in a discovery cohort (n=316), and validated these findings in an external SSc validation cohort (n=67). Cox regression was used to evaluate survival differences among groups. Gene expression profiles from skin biopsies from a subset of SSc patients (n=68) and controls (n=18) were analyzed with weighted gene co-expression network analyses to identify gene modules that were associated with cardiac pheno-groups and echocardiographic parameters.\n\nResultsFour SSc cardiac pheno-groups were identified with distinct profiles. Pheno-group #1 displayed a predominant cutaneous phenotype without cardiac involvement; pheno-group #2 had long-standing SSc with limited skin and cardiac involvement; pheno-group #3 had diffuse skin involvement, a high frequency of interstitial lung disease (88%), and significant right heart remodeling/dysfunction; and pheno-group #4 had prolonged SSc disease duration, limited skin involvement, and marked biventricular cardiac involvement. After multivariable adjustment, pheno-group #3 (hazard ratio [HR] 7.8, 95% confidence interval [CI] 1.5-33.0) and pheno-group #4 (HR 10.5, 95% CI 2.1-52.7) remained associated with mortality (P<0.05). The addition of pheno-group classification was additive to conventional survival models (P<0.05 by likelihood ratio test for all models), a finding that was replicated in the validation cohort. Skin gene expression analysis identified 2 gene modules (representing fibrosis and skin integrity, respectively) that differed among the cardiac pheno-groups and were associated with specific echocardiographic parameters.\n\nConclusionsMachine learning of echocardiographic and skin gene expression data in SSc identifies clinically relevant subgroups with distinct cardiac phenotypes, survival, and associated molecular pathways in skin.

genomics↗