Biology subjects

Ning, D.

Publications and source records attributed to Ning, D..

14 recordsLinked to original sources

bioRxiv2026

Enrichments along gradients resolve eco-evolutionary forces on subsurface microbiomes

How a single gram of soil harbors billions of microorganisms, each with distinct genomic variants that collectively maintain coherent ecological function(s), is one of microbiologys grand unsolved problems. A key obstacle is determining which variants contribute to individual- and community-level fitness, in which contexts, and how co-occurring ecotypes interact to divide niche space. Here, using nitrate (NO3-)-contaminated subsurface sediment as inoculum, we have performed high throughput enrichments in laboratory media of defined carbon source compositions across ecologically relevant gradients of pH and NO3-. Long-read metagenomics and link-community decomposition of co-occurrence networks of taxa across these enrichments has revealed context-specific functional interactions among dominant generalist and lower-abundance specialist denitrifier ecotypes that comprise 53 distinct enriched communities (EnComs) across 288 enrichments derived from a single sediment sample. We identified a single enzymatic difference of alternative NO3- reductases (NapAB vs. NarGHI) with differing substrate affinities that provided a mechanistic explanation for competitive niche partitioning between the two dominant taxa, Neorhizobium spp. and Allorhizobium spp., along the NO3- gradient. Genome-wide polymorphism ratios (pN/pS) revealed that selective pressures vary systematically with carbon source availability and gradients of pH and NO3-, which helps explain the natural biodiversity and functional interactions of ecotypes within denitrifying communities in the subsurface sediment. Our findings show that controlled enrichments along ecological gradients can thus uncover eco-evolutionary forces of selection, drift, and diversification that sculpt the biodiversity of microbial populations in the natural environment.

microbiology↗

bioRxiv2025

Viscoelastic HyA Hydrogel Promotes Recovery of Muscle Quality and Vascularization in a Murine Model of Delayed Rotator Cuff Repair

Rotator cuff tears are among the most common musculotendinous injuries with high risk of permanent functional disability. Following surgical repair, sub-optimal patient outcomes are directly correlated with poor muscle quality; namely, injury site fatty infiltration (FI), fibrosis, and muscle atrophy. Muscle resident fibro-adipogenic progenitor cells (FAPs) have been identified as key regulators of post-injury skeletal muscle regeneration and repair by maintaining a promyogenic environment. In this work, human-derived FAPs (hFAPs) were encapsulated into hyaluronic acid (HyA)-based hydrogels functionalized with bsp-RGD(15) cell adhesion peptide, heparin, and a matrix metalloproteinase (MMP)-cleavable crosslinker. Hydrogel-encapsulated hFAPs increased expression of the promyogenic marker UCP1 and production of the anti-inflammatory cytokine IL-10, while downregulating the expression of the fibrotic marker SMA over time. A murine model of unilateral rotator cuff transection, denervation, and delayed repair was treated with the HyA hydrogel or PBS and compared to a contralateral, non-injured control limb. Muscle histology 6 weeks post-repair revealed that the hydrogel reduced fibrosis, FI, and muscle atrophy while supporting vascularization of the injured tissue region. Collectively, these results suggest that the hydrogel alone can promote muscle regeneration in a clinically relevant delayed repair model of rotator cuff tear, which we hypothesize is due to controlled FAP differentiation into promyogenic lineages.

bioengineering↗

bioRxiv2024

Modest functional diversity decline and pronounced composition shifts of microbial communities in a uranium-contaminated aquifer

BackgroundMicrobial taxonomic diversity declines with increased environmental stress. Yet, few studies have explored whether phylogenetic and functional diversities track taxonomic diversity along the stress gradient. Here, we investigated bacterial communities within an aquifer in Oak Ridge, Tennessee, USA, which is characterized by a broad spectrum of stressors, including extremely high levels of nitrate, heavy metals like cadmium and chromium, radionuclides such as uranium, and extremely low pH (<3). ResultsBoth taxonomic and phylogenetic -diversities were reduced in the most impacted wells, while the decline in functional -diversity was modest and statistically insignificant, indicating a more robust buffering capacity to environmental stress. Differences in functional gene composition (i.e., functional {beta}-diversity) were pronounced in highly contaminated wells, while convergent functional gene composition was observed in uncontaminated wells. The relative abundances of most carbon degradation genes were decreased in contaminated wells, but genes associated with denitrification, adenylylsulfate reduction, and sulfite reduction were increased. Compared to taxonomic and phylogenetic compositions, environmental variables played a more significant role in shaping functional gene composition, suggesting that niche selection could be more closely related to microbial functionality than taxonomy. ConclusionsOverall, we demonstrated that despite a reduced taxonomic -diversity, microbial communities under stress maintained functionality underpinned by environmental selection.

microbiology↗

bioRxiv2024

Adipocyte progenitors are primary contributors to the disrupted epithelial niche that is sustained following abrupt mammary gland involution

A short duration of breastfeeding is a risk factor for the development of high-mortality, postpartum, triple-negative breast cancer. The intrinsic properties of cancer-initiating epithelial cells that persist following breastfeeding cessation and mammary gland remodeling are poorly understood. Previously, we showed that Platelet-Derived Growth Factor Receptor alpha (PDGFR)-expressing stromal mammary adipocyte progenitors (MAPs) differentiate into epithelial luminal progenitors in the adult gland. In the current study, we demonstrate that MAP-derived luminal progenitors retain a mesenchymal transcriptomic signature. In an abrupt involution model that mimics a short breastfeeding duration, MAP-derived luminal progenitors persist and dominate luminal epithelia, undergoing transcriptomic alterations that signify a distinct ferrometabolic state linked to cancer. Concurrently, MAPs adopt an alternative interferon-mediated profibrotic and invasive stromal fate. Our work uncovers MAPs to be the primary cellular origin of a pathological stromal and epithelial microenvironment following abrupt involution, presenting a potential therapeutic target in postpartum breast cancer.

cancer biology↗

bioRxiv2023

Obesity modifies cell fate plasticity of Pdgfrα-expressing mammary adipocyte progenitors to promote an aberrant mammary microenvironment

Excess fat gain culminating in obesity is a mounting global pandemic associated with a myriad of diseases including a higher risk of developing multiple cancers such as breast cancer. The underlying biological basis for obesity-linked breast cancer is attributed to alterations in adipose tissue-derived endocrine, metabolic and inflammatory factors. However, the precise cell types responsible for generating a cancer-susceptible mammary gland in obesity are not well understood. Using diet-induced obesity in conjunction with genetic reporter mouse models, we reveal elevated mammary adipocyte progenitors (MAPs) expressing Platelet-Derived Growth Factor Receptor alpha (PDGFR) in the mammary tissue microenvironment during obesity. Single-cell RNA sequencing analysis demonstrate intensified obesity-driven trajectories of MAPs to immune and epithelial progenitor cells. Further, lineage tracing indicates an invasive cellular state of MAPs that confers greater access of MAP descendants into the mammary epithelium concomitant with their transition into immune and epithelial cell fates. MAPs in obesity exhibit heightened activation of cancer-associated and inflammatory pathways where Egfr is identified as a common target upregulated in MAPs. Mechanistic studies on purified MAPs with a major obesity diet component and EGFR stimulation corroborate dynamic EGFR-mediated MAP responses. Our findings uncover MAPs as key contributors to forging an aberrant mammary gland in obesity, providing insight into the potential utility of targeting this cell lineage for eradicating cancer risk related to augmented adiposity.

cell biology↗

bioRxiv2023

A novel order-level lineage of ammonia-oxidizing Thaumarchaeota is widespread in marine and terrestrial environments

Ammonia-oxidizing archaea (AOA) are among the most ubiquitous and abundant groups of Archaea on Earth, widely distributed in marine, terrestrial, and geothermal ecosystems. However, the genomic diversity, biogeography, and evolutionary process of AOA populations in subsurface environments are vastly understudied compared to those of marine and soil AOA. We here report a novel AOA order Candidatus Nitrosomirales that forms a deeply branching basal sister lineage to the thermophilic Ca. Nitrosocaldales. Metagenomic and 16S rRNA gene read mapping demonstrates the dominant presence of Nitrosomirales AOA in various groundwater environments and their widespread distribution across a range of geothermal, terrestrial, and marine habitats. Notably, terrestrial Nitrosomirales AOA show the genetic capacity of using formate as an alternative source of reductant and appear to have acquired key metabolic genes and operons from other mesophilic populations via horizontal gene transfer, including the genes encoding urease, nitrite reductase, and V-type ATPase. Potential metabolic versatility and acquired functions may facilitate their radiation into a variety of subsurface, marine, and soil environments. Molecular thermometer-based evolutionary analysis suggests that Nitrosomirales originated from thermophilic environments and transitioned into temperate habitats in parallel with Nitrososphaerales and Nitrosopumilales. We also provide evidence that terrestrial-marine habitat transitions occurred within each one of the four AOA orders, which reveals a more complex evolutionary trajectory of major AOA lineages than previously proposed. Together, these findings establish a robust taxonomic and evolutionary framework of AOA and provide new insights into the ecology and evolution of this globally abundant functional guild.

microbiology↗

bioRxiv2022

MCIBox: A Toolkit for Single-molecule Multi-way Chromatin Interaction Visualization and Micro-Domains Identification

The emerging ligation-free three-dimensional (3D) genome mapping technologies can identify multiplex chromatin interactions with single-molecule precision. These technologies offer new insight into high-dimensional chromatin organization and gene regulation, but also introduce new challenges in data visualization and analysis. To overcome these challenges, we developed MCIBox, a toolkit for Multi-way Chromatin Interaction (MCI) analysis, including a visualization tool and a platform for identifying micro-domains with clustered single-molecule chromatin complexes. MCIBox is based on various clustering algorithms integrated with dimensionality reduction methods that can display multiplex chromatin interactions at single-molecule level, allowing users to explore chromatin extrusion patterns and super-enhancers regulation modes in transcription, and to identify single-molecule chromatin complexes that are clustered into micro-domains. Furthermore, MCIBox incorporates a two-dimensional kernel density estimation algorithm to identify micro-domains boundaries automatically. These micro-domains were stratified with distinctive signatures of transcription activity and contained different cell cycle associated genes. MCIBox could potentially distinguish the specificity of single-molecule chromatin interaction patterns in various phases of a cell cycle or cell types.

genomics↗

bioRxiv2022

EcoFun-MAP: An Ecological Function Oriented Metagenomic Analysis Pipeline

Annotating ecological functions of environmental metagenomes is challenging due to a lack of specialized reference databases and computational barriers. Here we present the Ecological Function oriented Metagenomic Analysis Pipeline (EcoFun-MAP) for efficient analysis of shotgun metagenomes in the context of ecological functions. We manually curated a reference database of EcoFun-MAP which is used for GeoChip design. This database included [~]1,500 functional gene families that were catalogued by important ecological functions, such as carbon, nitrogen, phosphorus, and sulfur cycling, metal homeostasis, stress responses, organic contaminant degradation, antibiotic resistance, microbial defense, electron transfer, virulence and plant growth promotion. EcoFun-MAP has five optional workflows from ultra-fast to ultra-conservative, fitting different research needs from functional gene exploration to stringent comparison. The pipeline is deployed on High Performance Computing (HPC) infrastructure with a highly accessible web-based interface. We showed that EcoFun-MAP is accurate and can process multi-million short reads in a minute. We applied EcoFun-MAP to analyze metagenomes from groundwater samples and revealed interesting insights of microbial functional traits in response to contaminations. EcoFun-MAP is available as a public web server at http://iegst1.rccc.ou.edu:8080/ecofunmap/.

bioinformatics↗

bioRxiv2021

Sustained ability of a natural microbial community to remove nitrate from groundwater

Microbial-mediated nitrate removal from groundwater is widely recognized as the predominant mechanism for nitrate attenuation in contaminated aquifers and is largely dependent on the presence of a carbon-bearing electron donor. The repeated exposure of a natural microbial community to an electron donor can result in the sustained ability of the community to remove nitrate; this phenomenon has been clearly demonstrated at the laboratory scale. However, in situ demonstrations of this ability are lacking. For this study, ethanol (electron donor) was repeatedly injected into a groundwater well (treatment) for six consecutive weeks to establish the sustained ability of a microbial community to remove nitrate. A second well (control) located up-gradient was not injected with ethanol during this time. The treatment well demonstrated strong evidence of sustained ability as evident by concomitant ethanol and nitrate removal and subsequent sulfate removal upon consecutive exposures. Both wells were then monitored for six additional weeks under natural (no injection) conditions. During the final week, ethanol was injected into both treatment and control wells. The treatment well demonstrated sustained ability as evident by concomitant ethanol and nitrate removal whereas the control did not. Surprisingly, the treatment well did not indicate a sustained and selective enrichment of a microbial community. These results suggested that the predominant mechanism(s) of sustained ability likely exist at the enzymatic- and/or genetic-levels. The results of this study demonstrated that the in situ ability of a microbial community to remove nitrate can be sustained in the prolonged absence of an electron donor. Moreover, these results implied that the electron-donor exposure history of nitrate-contaminated groundwater can play an important role nitrate attenuation. Article Impact StatementGroundwater microbes sustain ability to remove nitrate in absence of carbon and energy source.

ecology↗

bioRxiv2020

Conversion of marginal land into switchgrass conditionally accrues soil carbon and reduces methane consumption

Switchgrass (Panicum virgatum L.) is a perennial C4 grass native to tallgrass prairies of the Central US, and a promising bioenergy feedstock. Switchgrass can be cultivated on soils with low nutrient contents and its rooting depth, of up to 2 m, has brought attention to the crop as a potential mechanism to sequester and build soil carbon (C). Switchgrass, therefore, offers multifaceted benefits on degraded soils by enhancing soil organic matter content. However, to evaluate the sustainability of switchgrass-based biofuel production, it is crucial to understand the impacts of land conversion and switchgrass establishment on biotic/abiotic characteristics of various soils. In this study, we characterized the ecosystem-scale consequences of switchgrass growing at two highly-eroded, Dust Bowl remnant field sites from Oklahoma US, with silt-loam (SL) or clay-loam (CL) soil textures having low nitrogen (N), phosphorus (P), and C contents. Paired plots at each site, including fallow control and switchgrass-cultivated, were assessed. Our results indicated that switchgrass significantly increased soil C at the SL site and reduced microbial diversity at the CL site. The CL site exhibited significantly higher CO2 flux and higher respiration from switchgrass plots. Strikingly, switchgrass significantly reduced the CH4 consumption by an estimated 39% for the SL site and 47% for the CL site. Structural equation modeling identified soil temperature, P content, and soil moisture levels as the most influential factors regulating both CO2 and CH4 fluxes. CO2 flux was also influenced by microbial biomass while CH4 flux was influenced by microbial diversity. Together, our results suggest that site selection by soil type is a crucial factor in improving soil C stocks and mitigating greenhouse gas (GHG) fluxes, especially considering our finding that switchgrass reduced methane consumption, implying that carbon balance considerations should be accounted for to fully evaluate the sustainability of switchgrass cultivation.

molecular biology↗

bioRxiv2020

A quantitative framework reveals the ecological drivers of grassland soil microbial community assembly in response to warming

Unraveling the drivers controlling community assembly is a central issue in ecology. Selection, dispersal, diversification and drift are conceptually accepted as major community assembly processes. Defining their relative importance in governing biodiversity is compellingly needed, but very challenging. Here, we present a novel framework to quantitatively infer community assembly mechanisms by phylogenetic bin-based null model analysis (iCAMP). Our results with simulated microbial communities showed that iCAMP had high accuracy (0.93 - 0.99), precision (0.80 - 0.94), sensitivity (0.82 - 0.94), and specificity (0.95 - 0.98), which were 10-160% higher than those from the entire community-based approach. Applying it to grassland microbial communities in response to experimental warming, our analysis showed that homogeneous selection (38%) and "drift" (59%) played dominant roles in controlling grassland soil microbial community assembly. Interestingly, warming enhanced homogeneous selection, but decreased "drift" over time. Warming-enhanced selection was primarily imposed on Bacillales in Firmicutes, which were strengthened by increased drought and reduced plant productivity. This general framework should also be useful for plant and animal ecology.

ecology↗

bioRxiv2020

Lower Soil Carbon Loss Due to Persistent Microbial Adaptation to Climate Warming

Soil microbial respiration is an important source of uncertainty in projecting future climate and carbon (C) cycle feedbacks. Despite intensive studies for two decades, the magnitude, direction, and duration of such feedbacks are uncertain, and their underlying microbial mechanisms are still poorly understood. Here we examined the responses of soil respiration and microbial community structure to long-term experimental warming in a temperate grassland ecosystem. Our results indicated that the temperature sensitivity of soil microbial respiration (i.e., Q10) persistently decreased by 12.0{+/-}3.7% across 7 years of warming. Integrated metagenomic and functional analyses showed that microbial community adaptation played critical roles in regulating respiratory acclimation. Incorporating microbial functional gene abundance data into a microbially-enabled ecosystem model significantly improved the modeling performance of soil microbial respiration by 5-19%, compared to the traditional non-microbial model. Model parametric uncertainty was also reduced by 55-71% when gene abundances were used. In addition, our modeling analyses suggested that decreased temperature sensitivity could lead to considerably less heterotrophic respiration (11.6{+/-}7.5%), and hence less soil C loss. If such microbially mediated dampening effects occur generally across different spatial and temporal scales, the potential positive feedback of soil microbial respiration in response to climate warming may be less than previously predicted.

ecology↗

bioRxiv2019

Century long fertilization reduces stochasticity controlling grassland microbial community succession

Determining the drivers underlying ecological succession is a fundamental goal of ecological research and essential for predicting ecosystem functioning in response to human-induced environmental changes. Although various studies have examined the impacts of nitrogen (N) addition on plant and microbial community diversity, structure and activities, it remains unknown how long-term anthropogenic fertilization affects the ecological succession of microbial functional guilds and its underlying community assembly mechanisms. Here, using archived soils, we examined more than a centurys succession in soil microbial functional communities (from 1870 to 2008) from the Park Grass Experiment at Rothamsted Experimental Station, the longest running ecological experiment in the world. Long-term fertilization was found to significantly alter soil functional community structure and led to increasingly convergent succession of soil microbial communities. Meta-analysis indicated that microbial temporal turnover (w) was highly time scale-dependent, and the w value threshold was estimated as 0.0025 with a threshold time point of approximately 160 years. In addition, the importance of stochastic assembly varied greatly in regulating the succession of different microbial guilds. Fertilization had large to medium effects on reducing ecological stochasticity for microbial guilds involved in carbon (C) fixation and degradation, N fixation and mineralization, and denitrification. This century long-term study elucidated the differing influences of assembly mechanisms on soil microbial functional communities involved in C and N cycling, which could not be derived from taxonomic or phylogenetic approaches.

ecology↗

bioRxiv2017

Microbial community assembly differs by mineral type in the rhizosphere

Inputs of root carbon (C) fuel growth of nearby soil microorganisms. If these microbes associate with soil minerals, then mineral-microbiome complexes near roots could be a gateway towards stabilization of soil carbon and may influence the quantity and quality of persistent SOM. To investigate the interactions between roots, soil minerals, and microbes, we incubated three types of minerals (ferrihydrite, kaolinite, quartz) and a native soil mineral fraction near roots of a common Californian annual grass, Avena barbata, growing in its resident soil. We followed microbial colonization of these minerals for 2.5 months - the plants lifespan. Bacteria and fungi that colonized mineral surfaces during this experiment differed across mineral types and differed from those in the background soil, implying microbial colonization was the result of processes in addition to passive movement with water to mineral surfaces. Null model analysis revealed that dispersal limitation was a dominant factor structuring mineral-associated microbial communities for all mineral types. Once bacteria arrived at a mineral surface, capacity for rapid growth appeared important, as ribosomal copy number was significantly correlated with relative enrichment on minerals. Glomeromycota (a phylum associated with arbuscular mycorrhizal fungi) appeared to preferentially associate with ferrihydrite surfaces. The mechanisms enabling colonization of soil minerals may be foundational to the overall soil microbiome composition and partially responsible for the persistence of C entering soil via plant roots.

microbiology↗