Biology subjects

Hartman, S.

Publications and source records attributed to Hartman, S..

11 recordsLinked to original sources

bioRxiv2026

Adipose tissue as a site of immune activation and dysfunction in individuals with obesity and asthma

Obesity increases local inflammatory responses in adipose tissue. Individuals with obesity have increased asthma incidence and severity and reduced responses to asthma therapeutics through unknown mechanisms. To identify mechanisms by which increased fat mass augments asthma pathogenesis, single cell RNA sequencing of the immune-rich stromovascular fraction of subcutaneous adipose tissue was conducted from well-characterized adults with obesity-associated asthma matched to adults without asthma. Individuals with asthma had increased abundance of perivascular macrophages and lymphoid-associated macrophages (LAMs) and reduced abundance of classical monocytes and CD4+ and CD8+ naive T cells. Pseudo-bulk differential expression (DE) identified upregulation of cellular metabolism, specifically oxidative phosphorylation, and decreased immune homeostatic pathways in asthma across immune cell subsets. Cell type specific DE analysis of effector cell subtypes identified significant induction of metallothionein gene expression in asthma, a signature of immune cell dysfunction characterized by both an activation and exhaustion phenotype. Gene co-expression analysis identified gene modules associated with asthma diagnosis, lung function, and biomarkers of type 2 inflammation were enriched in effector cells. These data identify adipose tissue dysfunction occurs in obesity-associated asthma and support adipose tissue as therapeutic target to address the enhanced asthma risk among those with obesity. Grant SupportNIH U01AI155299, P30DK020593, R01AI182159, K23HL159351, UL1RR024975-03, P30CA68485, P30EY08126, G20RR030956, 5UL1TR002243, KL2TR002245, P30AI110527, DK020593, American Heart Association 17SFRN33520017.

immunology↗

bioRxiv2026

An oxygen-sensing Polycomb-group protein encodes flooding stress memory in plants

Most organisms, including plants, can encode stress memories that improve resilience to repeated environmental challenges. Flooding events expose plants to recurrent hypoxia, yet whether plants establish an adaptive memory of flooding is unclear. Here we show that somatic flooding stress memory is a conserved feature across multiple angiosperm species. In Arabidopsis, this memory depends on the oxygen-sensitive Polycomb Repressive Complex 2 (PRC2) subunit VERNALIZATION2 (VRN2). Loss of VRN2 impairs epigenetic memory formation and disrupts transcriptional memory at key genes that promote anthocyanin accumulation and repress leaf senescence, adaptive responses that enhance flooding tolerance. Collectively, we reveal a molecular mechanism where VRN2-PRC2 acts as both an oxygen sensor and chromatin effector to establish adaptive flooding stress memory in plants. ShortOur work defines a molecular mechanism for flooding stress memory in plants, actioned via the PRC2 subunit VRN2, that acts as the direct molecular (low) oxygen sensor and transducer. Coupled to its role in cold sensing, this identifies VRN2 as a master sensor subunit of the plant PRC2 that integrates multiple environmental cues to modulate the chromatin landscape and encode environmental memory.

plant biology↗

bioRxiv2026

The compartmentalized activity of a legume subtilase SBT12a allows symbiosome stabilization

The stabilization of rhizobia in specialized organelles, called symbiosomes, is an evolutionary hallmark for maintaining high rates of nitrogen fixation in legumes. This is achieved by releasing thousands of bacteria from nodular infection threads within in a single plant cell, which poses a great challenge for the host to keep control over these differentiated bacteria. Considering the importance of proteolytic degradation of antimicrobial proteins or generation of symbiosis-promoting peptides, proteolytic activity may represent a key regulatory system. Indeed, we identified the Medicago truncatula subtilisin-like protease (subtilase, SBT) 12a acting as a novel regulator of symbiosome functionality and maintenance. Loss-of-function mutations in SBT12a led to severe symbiotic defects with nodules of sbt12a being characterized by high level induction of defense/senescence-related genes. Using untargeted proteomic High-efficiency Undecanal-based N-Termini EnRichment (HUNTER) we identified and individually confirmed specific SBT12a target proteins that are involved in plant defense responses and symbiosome maintenance. This positions SBT12a as a central host factor controlling symbiosome performance.

plant biology↗

bioRxiv2025

Decitabine reverses innate immune gene suppression in rare melanomas

Rare melanoma subtypes, including acral, mucosal, and uveal melanomas, exhibit limited responses to immune checkpoint inhibitors (ICIs), yet the molecular mechanisms of immune resistance remain poorly defined. Here, we performed transcriptomic profiling of patient-derived xenografts (PDXs) and publicly available tumor datasets to systematically compare intratumoral gene expression across cutaneous and rare melanoma subtypes. We identified a convergent downregulation of innate immune pathogen sensing (IIPS) and type I interferon signaling pathways in rare melanomas compared to cutaneous, with lower expression also observed in anti-PD-1 non-responder tumors. CIBERSORT deconvolution of immune populations revealed that lower IIPS gene-expressing tumors exhibited reduced CD8 T cell and memory CD4 T cell infiltration, and enrichment of M2 macrophages, consistent with a more immunosuppressive tumor microenvironment. In vitro screening of epigenetic and immunomodulatory compounds revealed that the DNA hypomethylating agent decitabine robustly induced IIPS and adaptive immune gene expression in rare melanoma cell lines. In vivo treatment of mucosal and uveal melanoma xenograft models with decitabine resulted in durable upregulation of IIPS and antigen presentation genes, and whole transcriptome analysis confirmed that IIPS gene re-expression was the dominant transcriptional consequence of decitabine treatment. These findings highlight silencing of IIPS genes as a recurrent immune evasion mechanism in rare melanomas and nominate decitabine as a potential immunomodulatory strategy for enhancing immune responsiveness.

cancer biology↗

bioRxiv2025

Autophagic degradation of EIN3 ensures developmental plasticity and recovery from environmental stress in Arabidopsis

Ethylene signaling, mediated by the key transcription factor EIN3, regulates diverse developmental processes and stress adaptations, including hypocotyl growth, aging, and submergence tolerance. Autophagy, a cellular recycling process, also facilitates adaptation by reprogramming cellular components. While EIN3 degradation via the proteasome is well established, its connection to autophagy remains unclear. Here, we show that EIN3 turnover is directly regulated by ATG8-mediated autophagy. Consistently, autophagy-deficient plants exhibit impaired EIN3-dependent hypocotyl growth during light-to-dark transitions. Additionally, EIN3 accumulation contributes to the premature senescence observed in atg mutants. Beyond development, our combination of cell imaging, phenotypic analyses, and proteomics reveals that autophagy is essential for EIN3-driven transcriptional reprogramming during submergence. Together, our findings uncover a direct role for autophagy in regulating EIN3 stability, providing mechanistic insight into how this process fine-tunes ethylene responses in growth and stress adaptation.

plant biology↗

bioRxiv2024

VRN2-PRC2 facilitates light-triggered repression of PIF signalling to coordinate growth in Arabidopsis

The polycomb protein VERNALIZATION2 (VRN2) is a plant-specific subunit of the polycomb repressive complex 2 (PRC2), a conserved eukaryotic holoenzyme that represses gene expression by depositing the histone H3K27me3 mark in chromatin. Previous work established VRN2 as an oxygen-regulated target of the N-degron pathway that may function as a sensor subunit connecting PRC2 activity to the perception of positional and environmental cues. Here we show that VRN2 is enriched in hypoxic meristematic regions and emerging leaves of Arabidopsis under non-stressed conditions, and that vrn2 mutants are larger than wild type, indicating that VRN2-PRC2 negatively regulates growth and development. This growth phenotype is caused by ectopic expression of genes that promote cell expansion, including many SAUR genes and other direct PIF transcription factor targets. Analysis of SAUR19 promoter activity and expression dynamics revealed that VRN2 is required to specifically repress these genes in the light. Moreover, we show that VRN2 is epistatic to PIF4, and directly binds and methylates histones of key loci in the PIF4 transcriptional network to provide robust light-responsive control of gene expression and growth. We propose that hypoxia-stabilised VRN2-PRC2 sets a conditionally repressed chromatin state at PIF-regulated hub genes early in leaf ontogeny coinciding with the cell division phase, and that this is required for enhancing their subsequent repression via a light-responsive signalling cascade as cells enter the expansion phase. Thus, we have identified VRN2-PRC2 as core component of a spatially regulated and developmentally encoded epigenetic mechanism that co-ordinates environment-responsive growth by facilitating light-triggered suppression of PIF signalling.

plant biology↗

bioRxiv2024

MEDIATOR SUBUNIT 25 modulates ERFVII-controlled hypoxia responses in Arabidopsis

Flooding impairs plant growth through oxygen deprivation, which activates plant survival and acclimation responses. Low-oxygen responses are generally associated with activation of group VII ETHYLENE-RESPONSE FACTOR (ERFVII) transcription factors. However, mechanism and molecular components by which ERFVII factors initiate gene expression are not fully elucidated. Here, we show that the Mediator complex subunit AtMED25 is recruited by RELATED TO APETALA 2.2 (RAP2.2) and RAP2.12 to coordinate gene expression during hypoxia in Arabidopsis thaliana.. The med25 mutants display reduced low-oxygen stress tolerance. AtMED25 associates with several ERFVII-controlled hypoxia core genes and its loss impairs transcription under hypoxia due to decreasing RNA polymerase II recruitment. Protein complex pulldown assays demonstrate that the Mediator complex built around AtMED25 is adjusted under low-oxygen conditions. Moreover, during hypoxia, no functional cooperation between AtMED25 and the two subunits AtMED8 and AtMED16 occurs, contrasting previous observations made for other conditions. In addition, AtMED25 function under hypoxia is independent from ethylene signalling. Finally, a functional conservation at the molecular level was found for the MED25-ERFVII module between Arabidopsis thaliana and the monocot Oryza sativa, pointing to a potentially universal role of MED25 in enabling ERFVII-dependent transcript responses to hypoxia in plants.

plant biology↗

bioRxiv2024

Walk This Way: Modeling Foraging Ant Dynamics in Multiple Food Source Environments

Foraging for resources is an essential process for the daily life of an ant colony. What makes this process so fascinating is the self-organization of ants into trails using chemical pheromone in the absence of direct communication. Here we present a stochastic lattice model that captures essential features of foraging ant dynamics inspired by recent agent-based models while forgoing more detailed interactions that may not be essential to trail formation. Nevertheless, our models results coincide with those presented in more sophisticated theoretical models and experiment. Furthermore, it captures the phenomenon of multiple trail formation in environments with multiple food sources. This latter phenomenon is not described well by other more detailed models. An additional feature of this approach is the ability to derive a corresponding macroscopic PDE from the stochastic lattice model which can be described via first principle interactions and is amenable to analysis. Linear stability analysis of this PDE reveals the key biophysical parameters that give rise to trail formation. We also highlight universal features of the modeling framework that this simple formation may allow it to be used to study complex systems beyond ants.

ecology↗

bioRxiv2022

Ethylene augments root hypoxia tolerance through amelioration of reactive oxygen species and growth cessation

Flooded plants experience impaired gas diffusion underwater, leading to oxygen deprivation (hypoxia). The volatile plant hormone ethylene is rapidly trapped in submerged plant cells and is instrumental for enhanced hypoxia acclimation. However, the precise mechanisms underpinning ethylene-enhanced hypoxia survival remain unclear. We studied the effect of ethylene pre-treatment on hypoxia survival of primary Arabidopsis thaliana root tips. Both hypoxia itself and re-oxygenation following hypoxia are highly damaging to root tip cells and ethylene pre-treatments reduced this damage. Ethylene pre-treatment alone altered the abundance of transcripts and proteins involved in hypoxia responses, root growth, translation and reactive oxygen species (ROS) homeostasis. Through imaging and manipulating ROS abundance in planta, we demonstrate that ethylene limits excessive ROS formation during hypoxia and subsequent re-oxygenation and improves oxidative stress survival. In addition, we show that ethylene leads to rapid root growth cessation and this quiescence behaviour contributes to enhanced hypoxia tolerance. Collectively, our results show that the early flooding signal ethylene modulates a variety of processes that all contribute to hypoxia survival.

plant biology↗

bioRxiv2021

Combinations of Peptides Synergistically Activate the Regenerative Capacity of Skin Cells In Vitro

OBJECTIVETo explore synergistic effects related to skin regeneration, peptides with distinct biological mechanisms of action were evaluated in combination in different skin cell lines in the presence or absence of niacinamide (Nam). Furthermore, the synergistic responses of peptide combinations on global gene expression were compared to the changes that occur with fractional laser resurfacing treatment, a gold standard approach for skin rejuvenation, to further define optimal peptide combinations. METHODSMicroarray profiling was used to characterize the biological responses of peptide combinations (+/- Nam) relative to the individual components in epidermal keratinocyte and dermal fibroblast cell lines. Cellular functional assays were utilized to confirm the synergistic effects of peptide combinations. Bioinformatics approaches were used to link the synergistic effects of peptide combinations on gene expression to the transcriptomics of the skin rejuvenation response from fractional laser treatment. RESULTSMicroarray analysis of skin cells treated with peptide combinations revealed synergistic changes in gene expression compared to individual peptide controls. Bioinformatic analysis of synergy genes in keratinocytes revealed activation of NRF2-mediated oxidative stress responses by a combination of Ac-PPYL, Pal-KTTKS, and Nam. Additional analysis revealed direct downstream transcriptional targets of NRF2/ARE exhibiting synergistic regulation by this combination of materials, which was corroborated by a cellular reporter assay. NRF2-mediated oxidative stress response pathways were also found to be activated in the transcriptomics of the early skin rejuvenation response to fractional laser treatment, suggesting the importance of this biology in the early stages of tissue repair. Additionally, a second combination of peptides (pal-KT and Ac-PPYL) was found to synergistically restore cellular ATP levels that had been depleted due to the presence of ROS, indicating an additional mechanism whereby peptide synergies may accelerate skin repair. CONCLUSIONThrough combinatorial synergy studies, we have identified additional in vitro skin repair mechanisms beyond the previously described functions of individual peptides and correlated these to the transcriptomics of the skin rejuvenation response of fractional laser treatment. These findings suggest that specific peptides can act together, via complementary and synergistic mechanisms, to holistically enhance the regenerative capacity of in vitro skin cells.

molecular biology↗

bioRxiv2019

Ethylene-mediated nitric oxide depletion pre-adapts plants to hypoxia stress

Timely perception of adverse environmental changes is critical for survival. Dynamic changes in gases are important cues for plants to sense environmental perturbations, such as submergence. In Arabidopsis thaliana, changes in oxygen and nitric oxide (NO) control the stability of ERFVII transcription factors. ERFVII proteolysis is regulated by the N-degron pathway and mediates adaptation to flooding-induced hypoxia. However, how plants detect and transduce early submergence signals remains elusive. Here we show that plants can rapidly detect submergence through passive ethylene entrapment and use this signal to pre-adapt to impending hypoxia. Ethylene can enhance ERFVII stability prior to hypoxia by increasing the NO-scavenger PHYTOGLOBIN1. This ethylene-mediated NO depletion and consequent ERFVII accumulation pre-adapts plants to survive subsequent hypoxia. Our results reveal the biological link between three gaseous signals for the regulation of flooding survival and identifies novel regulatory targets for early stress perception that could be pivotal for developing flood-tolerant crops.

plant biology↗