Biology subjects

Fennell, A.

Publications and source records attributed to Fennell, A..

11 recordsLinked to original sources

bioRxiv2026

Senescent cell networks link matrix remodeling and vascular dysfunction in human fibroids

Uterine fibroids (leiomyomas) are highly prevalent benign tumors defined by excessive extracellular matrix (ECM) deposition, altered vascular structure, and progressive tissue stiffening, yet the cellular programs that coordinate these features remain poorly understood. Cellular senescence has been implicated in fibroid biology, but whether senescence represents a uniform state or distinct, functionally specialized cell identities within fibroids is unknown. Here, we identify the distinct heterogeneous populations of senescent cells ("senotypes") present in human fibroids and characterize their role in shaping the fibroid microenvironment. Using single-cell RNA sequencing (scRNA-seq) integrated with a senescence gene signature and protein-level validation, we identify senescent cells (SnC) distributed across fibroblast, mural, and endothelial compartments, each exhibiting distinct transcriptional programs. SnC endothelial cells (ECs) are enriched in fibroids relative to matched myometrium and activate TEAD4-associated mechanosensing, angiogenic, and immune signaling pathways, despite being associated with impaired vessel maturation in situ. In parallel, SnC fibroblast and mural populations in fibroids upregulated SRF-associated cytoskeletal and ECM programs, accompanied by increased COL6A3 expression and collagen VI deposition, consistent with tissue stiffening. Ligand-receptor and spatial analyses reveal that these SnC populations function as interconnected signaling hubs, coordinating immune cell recruitment and stromal remodeling. Importantly, analysis of human fibroids treated with collagenase demonstrated a reduction in both ECM density and SnC burden, supporting a reinforcing relationship between matrix mechanics and senescence. Together, these findings establish senescence in fibroids as a heterogeneous, mechanically reinforced, and network-driven process that links vascular dysfunction, immune signaling, and fibrosis, highlighting distinct SnC states as potential translational targets for non-surgical therapies.

cell biology↗

bioRxiv2026

PhytoFam: A Nextflow Pipeline for Genome-Wide Analysis of Plant Gene Families

Genome-wide identification of plant gene families is essential for functional and evolutionary studies but often requires the use of multiple independent tools for homolog detection, domain validation, orthology assignment, and phylogenetic analysis. This fragmented approach involves extensive manual scripting, complicates reproducibility and parameter tracking, and may require additional steps to remove redundant protein isoforms. To address these challenges, we developed PhytoFam, a Nextflow-based workflow that automates gene family identification from proteome input through phylogenetic reconstruction. The pipeline integrates HMMER for candidate sequence identification, isoform-aware deduplication, InterProScan for domain confirmation, BLAST reciprocal best hit (RBH) analysis for orthology assignment, MUSCLE for multiple sequence alignment with optional outgroup incorporation, TrimAl for alignment trimming, and IQ-TREE3 for phylogenetic reconstruction. PhytoFam is portable across local workstations and high-performance computing environments and supports deployment through Conda, Docker, and Singularity. We validated the workflow using the Morus alba MADS-box gene family, where the complete analysis finished in 1 h 10 min (9 CPU h). IQ-TREE3 accounted for most of the execution time, whereas InterProScan showed the highest memory requirement with a peak resident set size of 4.5 GB. PhytoFam provides a reproducible, automated, and scalable solution for plant gene family identification and phylogenetic analysis. The pipeline is freely available at https://github.com/sanamparajuli/PhytoFam.

bioinformatics↗

bioRxiv2026

Acute priming using elevated fluid viscosity recovers young-like single-cellsurveillance behaviors in aged human T cells

Aging is a complex biological process, often characterized by increased vulnerability to disease, infection, and death. This increased vulnerability is mechanistically linked to a progressive and functional decline of the immune system. In humans, aged lymphocytes lose their capacity to effectively surveil within diverse microenvironments, decreasing their capability for clearing infections and maintaining physiological homeostasis. However, specific mechanisms by which aged lymphocytes, specifically T cells, lose this capacity to surveil remain unclear. We profiled three core characteristics of T cell surveillance at single-cell resolution, specifically migration, deformability, and sensing. While aged T cells retained their capacity for spontaneous migration, they exhibited impaired cellular deformability and deficiencies in sensing local signaling cues. To modulate this surveillance defect, we performed mechanical reprogramming using elevated fluid viscosity. Results showed that acute priming of aged T cells with elevated fluid viscosity recovered a transient young-like surveillance phenotype, which was mechanistically linked to membrane tension, cortical F-actin, and Arp3 expression. These findings reveal a key source of surveillance defects in aged T cells and provide an effective mechanical approach to tuning their single-cell behaviors. TeaserRecovery of young-like surveillance phenotypes in aging human T cells via viscosity priming

bioengineering↗

bioRxiv2024

Self-organizing ovarian somatic organoids preserve cellular heterogeneity and reveal cellular contributions to ovarian aging

Ovarian somatic cells are essential for reproductive function, but no existing ex vivo models recapitulate the cellular heterogeneity or interactions within this compartment. We engineered a novel ovarian somatic organoid model by culturing a stroma-enriched fraction of mouse ovaries in scaffold-free agarose micromolds. Ovarian somatic organoids self-organized, maintained diverse cell populations, produced extracellular matrix, and secreted hormones. Organoids generated from reproductively old mice exhibited reduced aggregation and growth compared to young counterparts, as well as differences in cellular composition. Interestingly, matrix fibroblasts from old mice demonstrated upregulation of pathways associated with the actin cytoskeleton and downregulation of cell adhesion pathways, indicative of increased cellular stiffness which may impair organoid aggregation. Cellular morphology, which is regulated by the cytoskeleton, significantly changed with age and in response to actin depolymerization. Moreover, actin depolymerization rescued age-associated organoid aggregation deficiency. Overall, ovarian somatic organoids have advanced fundamental knowledge of cellular contributions to ovarian aging.

cell biology↗

bioRxiv2023

Genome assembly of the hybrid grapevine Vitis Chambourcin

Background Chambourcin is a French-American interspecific hybrid grape variety grown in the eastern and midwestern United States and used for making wine. Currently, there are few genomic resources available for hybrid grapevines like Chambourcin. ResultsWe assembled the genome of Chambourcin using PacBio HiFi long-read sequencing, Bionano optical map sequencing and Illumina short read sequencing. We produced an assembly for Chambourcin with 26 scaffolds with an N50 length of 23.3 Mb and an estimated BUSCO completeness of 97.9%. 33,791 gene models were predicted, of which 81% (27,075) were functionally annotated using Gene Ontology and KEGG pathway analysis. We identified 16,056 common orthologs between Chambourcin gene models, V. vinifera PN40024 12X.v2, VCOST.v3, Shine Muscat (Vitis labruscana x V. vinifera) and V. riparia Gloire. A total of 1,606 plant transcription factors representing 58 different gene families were identified in Chambourcin. Finally, we identified 304,571 simple sequence repeats (SSRs), repeating units of 1-6 base pairs in length in the Chambourcin genome assembly. ConclusionsWe present the genome assembly, genome annotation, protein sequences and coding sequences reported for Chambourcin. The Chambourcin genome assembly provides a valuable resource for genome comparisons, functional genomic analysis and genome-assisted breeding research.

bioinformatics↗

bioRxiv2022

Grapevine leaf size influences vine canopy temperature

PremiseGrapevine leaves have diverse shapes and sizes. Their shape and size is known to be influenced by many factors including genetics, vine phytosanitary status, environment, leaf and vine age, and node position on the shoot. In order to determine the importance of grapevine leaf shape and size to canopy temperature, we examined the relationship in five seedling populations grown in a vineyard in California, USA. MethodsAll of the populations had one parent with compound leaves of the Vitis piasezkii type and each population had a different second parent with non-compound leaves. In previous work, we measured leaf shape and size using 21 homologous landmarks. Here, we paired these morphology data with measurements taken using an infrared thermometer to measure the temperature of the canopy. By recording time of sampling and canopy temperature, we were able to determine which vines were cooler or hotter than expected, using a linear model. ResultsWe established a relationship between leaf size and canopy temperature: vines with larger leaves were cooler than expected. In contrast, leaf shape was not strongly correlated with variation in temperature. ConclusionsUltimately, these findings indicate that vines with larger leaves may contribute to the reduction of overall vine canopy temperature, but further work is needed to determine if this is due to variation in leaf size, differences in the openness of the canopy, or other related traits.

plant biology↗

bioRxiv2022

Increases in vein length compensate for leaf area lost to lobing in grapevine

PremiseThere is considerable variation in leaf lobing and leaf size, including among grapevines, some of the most well-studied leaves. We examined the relationship between leaf lobing and leaf size across grapevine populations which varied in extent of leaf lobing. MethodsWe used homologous landmarking techniques to measure 2,632 leaves across two years in 476 unique, genetically distinct grapevines from 5 biparental crosses which vary primarily in the extent of lobing. We determined to what extent leaf area could explain variation in lobing, vein length, and vein to blade ratio. ResultsAlthough lobing was the primary source of variation in shape across the leaves we measured, leaf area varied only slightly as a function of lobing. Rather, leaf area increases as a function of total major vein length, total branching vein length, and decreases as a function of vein to blade ratio. These relationships are stronger for more highly lobed leaves, with the residuals for each model differing as a function of distal lobing. ConclusionsFor a given leaf area, more highly lobed leaves have longer veins and higher vein to blade ratios, allowing them to maintain similar leaf areas despite increased lobing. These findings show how more highly lobed leaves may compensate for what would otherwise result in a reduced leaf area, allowing for increased photosynthetic capacity through similar leaf size.

plant biology↗

bioRxiv2021

Endurance Exercise to Improve Physical Function in Adult and Older Mice: High Intensity Interval Training (HIIT) versus Voluntary Wheel Running (VWR)

With age comes a gradual decline in physical function and exercise capacity, concurrent with a progressive propensity for development of sarcopenia /(age-related loss of muscle mass and strength) and frailty (inability of body to thrive and maintain homeostasis). Prior research has demonstrated that exercise, while not a cure, can help mitigate sarcopenia/frailty and restore functional capacity. Reliable, validated, pre-clinical models are necessary to elucidate the underlying molecular mechanisms at the intersection of age, exercise, and functional decline. In this study, we hypothesized that endurance exercise programs mimicking typical human exercise protocols would improve physical function in both adult and older adult mice. Furthermore, our secondary hypothesis was that older mice would receive less benefit from a similar volume of exercise than adult mice. To test these hypotheses, we randomly assigned (with some selection criteria) male C57BL/6 mice either at adult ages during the study (n=24, designated 10m, aged 6 months to 10 months) or at older adult ages (n=18, designated 26m, aged 22 months to 26 months) to a 13-week program of voluntary wheel running (VWR, group termed RUN) or high intensity interval training (HIIT), with an additional 10m sedentary control (CON). The functional aptitude of each mouse was determined pre- and post-training using our composite CFAB (comprehensive functional assessment battery) scoring system consisting of voluntary wheel running (volitional exercise and activity rate), treadmill (endurance), rotarod (overall motor function), grip meter (forelimb strength), and inverted cling (whole body strength/endurance). To measure sarcopenia, we tracked body mass and body composition changes with EchoMRI, and measured muscle wet mass post-training.

physiology↗

bioRxiv2020

Root system influence on high dimensional leaf phenotypes over the grapevine growing season

O_LIIn many perennial crops, grafting the root system of one individual to the shoot system of another individual has become an integral part of propagation performed at industrial scales to enhance pest, disease, and stress tolerance and to regulate yield and vigor. Grafted plants offer important experimental systems for understanding the extent and seasonality of root system effects on shoot system biology. C_LIO_LIUsing an experimental vineyard where a common scion Chambourcin is growing ungrafted and grafted to three different rootstocks, we explore associations between root system genotype and leaf phenotypes in grafted grapevines across a growing season. We quantified five high-dimensional leaf phenotyping modalities: ionomics, metabolomics, transcriptomics, morphometrics, and physiology and show that rootstock influence is subtle but ubiquitous across modalities. C_LIO_LIWe find strong signatures of rootstock influence on the leaf ionome, with unique signatures detected at each phenological stage. Moreover, all phenotypes and patterns of phenotypic covariation were highly dynamic across the season. C_LIO_LIThese findings expand upon previously identified patterns to suggest that the influence of root system on shoot system phenotypes is complex and broad understanding necessitates volumes of high-dimensional, multi-scale data previously unmet. C_LI

plant biology↗

bioRxiv2018

Rootstock effects on scion phenotypes in a ‘Chambourcin’ experimental vineyard

Understanding how root systems modulate shoot system phenotypes is a fundamental question in plant biology and will be useful in developing resilient agricultural crops. Grafting is a common horticultural practice that joins the roots (rootstock) of one plant to the shoot (scion) of another, providing an excellent method for investigating how these two organ systems affect each other. In this study, we use the French-American hybrid grapevine Chambourcin (Vitis L.) as a model to explore the rootstock-scion relationship. We examined leaf shape, ion concentrations, and gene expression in Chambourcin grown own-rooted as well as grafted to three different rootstocks ( SO4, 1103P and 3309C) across two years and three different irrigation treatments. Results described here demonstrate that 1) the largest source of variation in leaf shape stems from the interaction of rootstock by irrigation; 2) leaf position, but also rootstock and rootstock by irrigation interaction, are the primary sources of variation in leaf ion concentrations; and 3) gene expression in scion leaves exhibited significantly different patterns of gene expression from ungrafted vines, and these expression patterns were rootstock-specific. Our work provides an initial description of the subtle and complex effect of grafting on Chambourcin leaf morphology, ionomics and gene expression in grapevine scions. Further work across multiple years, environments and additional phenotypes is required in order to determine how the relationship between the rootstock and the scion can best be leveraged for adapting grapevines to a changing climate.

plant biology↗

bioRxiv2018

IRIS-DGE: An integrated RNA-seq data analysis and interpretation system for differential gene expression

MotivationNext-Generation Sequencing has made available much more large-scale genomic and transcriptomic data. Studies with RNA-sequencing (RNA-seq) data typically involve generation of gene expression profiles that can be further analyzed, many times involving differential gene expression (DGE). This process enables comparison across samples of two or more factor levels. A recurring issue with DGE analyses is the complicated nature of the comparisons to be made, in which a variety of factor combinations, pairwise comparisons, and main or blocked main effects need to be tested.\n\nResultsHere we present a tool called IRIS-DGE, which is a server-based DGE analysis tool developed using Shiny. It provides a straightforward, user-friendly platform for performing comprehensive DGE analysis, and crucial analyses that help design hypotheses and to determine key genomic features. IRIS-DGE integrates the three most commonly used R-based DGE tools to determine differentially expressed genes (DEGs) and includes numerous methods for performing preliminary analysis on user-provided gene expression information. Additionally, this tool integrates a variety of visualizations, in a highly interactive manner, for improved interpretation of preliminary and DGE analyses.\n\nAvailabilityIRIS-DGE is freely available at http://bmbl.sdstate.edu/IRIS/.\n\nContactqin.ma@sdstate.edu\n\nSupplementary informationSupplementary data are available at Bioinformatics online.

bioinformatics↗