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All sourcesNASA NTRSDOE OSTI
DOE OSTI2026

Single-cell and spatial omics in plants: from cellular atlases to regulatory mechanisms

Single-cell RNA sequencing (scRNA-seq) has transformed transcriptomic studies by enabling gene expression profiling at the resolution of individual cells within and across a broad range of tissue types, revealing cellular heterogeneity that is obscured in bulk tissue transcriptomes. Over the past decade, improvements in microfluidics and library preparation have drastically increased throughput, allowing tens of thousands of cells to be assayed in a single experiment. Although initially developed in animal systems, scRNA-seq has rapidly emerged as a powerful and widely adopted approach in plant biology. Beyond transcriptomics, the integration of single-cell data with chromatin accessibility, proteomics, metabolomics, and spatial omics is enabling a system-level understanding of plant gene regulation and cellular organization. Network-based analytical frameworks further support the reconstruction of gene regulatory networks and the interpretation of complex single-cell data. In this review, we summarize the current technological landscape of plant single-cell studies, discuss key experimental and analytical challenges, and review emerging strategies for validating single-cell discoveries. We also discuss future directions in applying single-cell technologies to woody perennials plants and bioenergy-relevant crops, emphasizing their potential to accelerate the discovery of cell type-specific regulatory mechanisms underlying growth, stress resilience, and biomass production.

Li, Miaomiao [ORNL] (ORCID:0000000321326168)↗
DOE OSTI2026

spammR: an R package designed for analysis and integration of spatial multi-omic measurements

Spatial omics is a young and evolving field and as such shows rapid development of novel technologies and analysis methods to measure transcripts, proteins, metabolites, and post-translational modifications at high spatial resolution. These advances in technology have enabled the simultaneous generation of abundance profiles for multiple different omics types and associated microscopy imaging data, as well as their analysis in a spatial context. However, most analytical tools are designed for spatial transcriptomics platforms and are challenging to use in other contexts such as mass spectrometry-based measurements or metagenomics. To this end we present spammR (spatial analysis of multi-omics measurements in R), an R package that enables end-to-end analysis with a specific focus on mass-spectrometry derived spatial omics datasets with (1) smaller sample sizes and spatial sparsity of samples, (2) considerable missingness, and (3) no a-priori knowledge about proteins or genes of interest, relying on a fully data-driven approach.

spammR↗
DOE OSTI2024

From single cell to spatial multi-omics: unveiling molecular mechanisms in dynamic and heterogeneous systems

Single-cell multi-omics and spatial technology have been widely applied to biomedical studies and recently to environmental studies. Here, the cell size detected by single-cell omics ranges from ~2 µm (e.g., Bacillus subtilis) to ~120 µm (e.g., human oocytes). Simultaneous detection of single-cell multi-omics is available to human and plant tissues while limited to microbial samples. Spatial technology enables mapping the detected biomolecules in situ. The recent advances in MALDI-MSI and micro/nanoPOTS for the first time allow the application of spatial multi-omics in highly heterogeneous environmental samples composed of plants, fungi, and bacteria. We envision that these technologies will continue to advance our understanding of unique cell types, their developmental trajectory, and the intercellular signaling and interaction within biological samples.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Spatial Proteomics towards cellular Resolution

Introduction: Spatial biology is an emerging interdisciplinary field facilitating biological discoveries through the use of spatial omics technologies. Recent advancements in spatial transcriptomics, spatial genomics (e.g. genetic mutations and epigenetic marks), multiplexed immunofluorescence, and spatial metabolomics/lipidomics have enabled high-resolution spatial profiling of gene expression, genetic variation, protein expression, and metabolites/lipids profiles in tissue. These developments contribute to a deeper understanding of the spatial organization within tissue microenvironments at the molecular level. Areas covered: This report provides an overview of the untargeted, bottom-up mass spectrometry (MS)-based spatial proteomics workflow. It highlights recent progress in tissue dissection, sample processing, bioinformatics, and liquid chromatography (LC)-MS technologies that are advancing spatial proteomics toward cellular resolution. Expert opinion: The field of untargeted MS-based spatial proteomics is rapidly evolving and holds great promise. To fully realize the potential of spatial proteomics, it is critical to advance data analysis and develop automated and intelligent tissue dissection at the cellular or subcellular level, along with high-throughput LC-MS analyses of thousands of samples. In conclusion, achieving these goals will necessitate significant advancements in tissue dissection technologies, LC-MS instrumentation, and computational tools.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Challenges in spatial metabolomics and proteomics for functional tissue unit and single-cell resolution

While transcriptomics is the most broadly applied technology for global spatial and single cell measurements in healthy and diseased tissues. Transcripts are often used as a proxy for protein and even metabolite measurements, but it has become commonly accepted that extrapolating this kind of information is a poor proxy and not a substitute for direct measurement. Within the last decade advanced developments of mass spectrometry-based assays have made these direct measurements not only possible, but routine. Where mass spectrometry has become an enabling technology, and various methods can now detect hundreds of metabolites and thousands of proteins from samples. Not only can this be performed within bulk measurements, but much effort has been directed into translating these measurements to single cells and tissues at cellular resolution. The information obtained from mass spectrometry is now able to trace metabolic events and decipher feedback loops across anatomical regions, connecting genetic and metabolic networks that define phenotypes. Herein, we will broadly overview developments in the field over the past decade, leading into several case studies which highlight the direct measurement of metabolites, proteins, and proteoforms from thinly sliced tissues. Much of this work is feasible due to multidisciplinary team science, and we offer brief perspective on paths forward and the challenges that persist with adoption and application of spatial omics.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Exploring new frontiers in type 1 diabetes through advanced mass-spectrometry-based molecular measurements

Type 1 diabetes (T1D) is a devastating autoimmune disease for which advanced mass spectrometry (MS) methods are increasingly used to identify new biomarkers and better understand underlying mechanisms. For example, integration of MS analysis and machine learning has identified multimolecular biomarker panels. In mechanistic studies, MS has contributed to the discovery of neoepitopes, and pathways involved in disease development and identifying therapeutic targets. However, challenges remain in understanding the role of tissue microenvironments, spatial heterogeneity, and environmental factors in disease pathogenesis. Recent advancements in MS, such as ultra-fast ion-mobility separations, and single-cell and spatial omics, can play a central role in addressing these challenges. Here, in this work, we review recent advancements in MS-based molecular measurements and their role in understanding T1D.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

Spatiotemporal metabolic responses to water deficit stress in distinct leaf cell-types of poplar

The impact of water-deficit (WD) stress on plant metabolism has been predominantly studied at the whole tissue level. However, plant tissues are made of several distinct cell types with unique and differentiated functions, which limits whole tissue ‘omics’-based studies to determine only an averaged molecular signature arising from multiple cell types. Advancements in spatial omics technologies provide an opportunity to understand the molecular mechanisms underlying plant responses to WD stress at distinct cell-type levels. Here, we studied the spatiotemporal metabolic responses of two poplar ( Populus tremula× P. alba ) leaf cell types -palisade and vascular cells- to WD stress using matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI). We identified unique WD stress-mediated metabolic shifts in each leaf cell type when exposed to early and prolonged WD stresses and recovery from stress. During water-limited conditions, flavonoids and phenolic metabolites were exclusively accumulated in leaf palisade cells. However, vascular cells mainly accumulated sugars and fatty acids during stress and recovery conditions, respectively, highlighting the functional divergence of leaf cell types in response to WD stress. By comparing our MALDI-MSI metabolic data with whole leaf tissue gas chromatography-mass spectrometry (GC-MS)-based metabolic profile, we identified only a few metabolites including monosaccharides, hexose phosphates, and palmitic acid that showed a similar accumulation trend at both cell-type and whole leaf tissue levels. Overall, this work highlights the potential of the MSI approach to complement the whole tissue-based metabolomics techniques and provides a novel spatiotemporal understanding of plant metabolic responses to WD stress. This will help engineer specific metabolic pathways at a cellular level in strategic perennial trees like poplars to help withstand future aberrations in environmental conditions and to increase bioenergy sustainability.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

First Plant Cell Atlas symposium report

The Plant Cell Atlas (PCA) community hosted a virtual symposium on December 9 and 10, 2021 on single cell and spatial omics technologies. The conference gathered almost 500 academic, industry, and government leaders to identify the needs and directions of the PCA community and to explore how establishing a data synthesis center would address these needs and accelerate progress. This report details the presentations and discussions focused on the possibility of a data synthesis center for a PCA and the expected impacts of such a center on advancing science and technology globally. Community discussions focused on topics such as data analysis tools and annotation standards; computational expertise and cyber-infrastructure; modes of community organization and engagement; methods for ensuring a broad reach in the PCA community; recruitment, training, and nurturing of new talent; and the overall impact of the PCA initiative. These targeted discussions facilitated dialogue among the participants to gauge whether PCA might be a vehicle for formulating a data synthesis center. The conversations also explored how online tools can be leveraged to help broaden the reach of the PCA (i.e., online contests, virtual networking, and social media stakeholder engagement) and decrease costs of conducting research (e.g., virtual REU opportunities). Major recommendations for the future of the PCA included establishing standards, creating dashboards for easy and intuitive access to data, and engaging with a broad community of stakeholders. The discussions also identified the following as being essential to the PCA's success: identifying homologous cell-type markers and their biocuration, publishing datasets and computational pipelines, utilizing online tools for communication (such as Slack), and user-friendly data visualization and data sharing. In conclusion, the development of a data synthesis center will help the PCA community achieve these goals by providing a centralized repository for existing and new data, a platform for sharing tools, and new analytical approaches through collaborative, multidisciplinary efforts. A data synthesis center will help the PCA reach milestones, such as community-supported data evaluation metrics, accelerating plant research necessary for human and environmental health.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Editorial overview: Unlocking the secrets of nongenetic plasticity, one cell at a time

Cellular noise, the non-genetic variability observed among isogenic cells, arises from factors such as growth conditions, aging, and stochastic gene expression, influencing cell stress-response, metabolism, morphology, and size. Here, such plasticity, while critical for adaptation, often goes unnoticed with traditional population-averaging biotechnologies that inevitably mask cell-specific variations and prompting the question, "What else might we be missing". However, recent breakthroughs in optical imaging, microfluidics, and omics, are beginning to uncover the complexity of cellular plasticity. This special is-sue highlights some of these breakthroughs, with key contributions including innovations in multimodal chemical imaging, label-free microscopy, spatial and temporal omics, and droplet-based microfluidics. Collectively, these cutting-edge tools provide unprecedent-ed insights into non-genetic cell-to-cell variability, enhancing our understanding of cellu-lar plasticity and its implications for health, energy, and ecology.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Advanced multi-modal mass spectrometry imaging reveals functional differences of placental villous compartments at microscale resolution

The placenta is a complex and heterogeneous organ that links the mother and fetus, playing a crucial role in nourishing and protecting the fetus throughout pregnancy. Integrative spatial multi-omics approaches can provide a systems-level understanding of molecular changes underlying the mechanisms leading to the histological variations of the placenta during healthy pregnancy and pregnancy complications. Herein, we advance our metabolome-informed proteome imaging (MIPI) workflow to include lipidomic imaging, while also expanding the molecular coverage of metabolomic imaging by incorporating on-tissue chemical derivatization (OTCD). The improved MIPI workflow advances biomedical investigations by leveraging state-of-the-art molecular imaging technologies. Lipidome imaging identifies molecular differences between two morphologically distinct compartments of a placental villous functional unit, syncytiotrophoblast (STB) and villous core. Next, our advanced metabolome imaging maps villous functional units with enriched metabolomic activities related to steroid and lipid metabolism, outlining distinct molecular distributions across morphologically different villous compartments. Complementary proteome imaging on these villous functional units reveals a plethora of fatty acid- and steroid-related enzymes uniquely distributed in STB and villous core compartments. Integration across our advanced MIPI imaging modalities enables the reconstruction of active biological pathways of molecular synthesis and maternal-fetal signaling across morphologically distinct placental villous compartments with micrometer-scale resolution.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2025

Imaging and spatially resolved mass spectrometry applications in nephrology

The application of spatially resolved mass spectrometry (MS) and MS imaging approaches for studying biomolecular processes in the kidney is rapidly growing. These powerful methods, which enable label-free and multiplexed detection of many molecular classes across omics domains (including metabolites, drugs, proteins and protein post-translational modifications), are beginning to reveal new molecular insights related to kidney health and disease. Further, the complexity of the kidney often necessitates multiple scales of analysis for interrogating biofluids, whole organs, functional tissue units, single cells and subcellular compartments. Various MS methods can generate omics data across these spatial domains and facilitate both basic science and pathological assessment of the kidney. Optimal processes related to sample preparation and handling for different MS applications are rapidly evolving. Emerging technology and methods, improvement of spatial resolution, broader molecular characterization, multimodal and multiomics approaches and the use of machine learning and artificial intelligence approaches promise to make these applications even more valuable in the field of nephology. Overall, spatially resolved MS and MS imaging methods have the potential to fill much of the omics gap in systems biology analysis of the kidney and provide functional outputs that cannot be obtained using genomics and transcriptomic methods.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

An optimized approach and inflation media for obtaining complimentary mass spectrometry-based omics data from human lung tissue

Human disease states are biomolecularly multifaceted and can span across phenotypic states, therefore it is important to understand diseases on all levels, across cell types, and within and across microanatomical tissue compartments. To obtain an accurate and representative view of the molecular landscape within human lungs, this fragile tissue must be inflated and embedded to maintain spatial fidelity of the location of molecules and minimize molecular degradation for molecular imaging experiments. Here, we evaluated agarose inflation and carboxymethyl cellulose embedding media and determined effective tissue preparation protocols for performing bulk and spatial mass spectrometry-based omics measurements. Mass spectrometry imaging methods were optimized to boost the number of annotatable molecules in agarose inflated lung samples. This optimized protocol permitted the observation of unique lipid distributions within several airway regions in the lung tissue block. Laser capture microdissection of these airway regions followed by high-resolution proteomic analysis allowed us to begin linking the lipidome with the proteome in a spatially resolved manner, where we observed proteins with high abundance specifically localized to the airway regions. We also compared our mass spectrometry results to lung tissue samples preserved using two other inflation/embedding media, but we identified several pitfalls with the sample preparation steps using this preservation method. Overall, we demonstrated the versatility of the inflation method, and we can start to reveal how the metabolome, lipidome, and proteome are connected spatially in human lungs and across disease states through a variety of different experiments.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

RhizoGrid Indexed Sorghum Rhizosphere Multi-Omics

PerCon SFA project data dentification of spatially resolved biomarkers of drought in Sorghum bicolor rhizosphere molecular-microbe interactions using a novel root cartography "RhizoGrid" system for sampling plants under drought and control conditions across 10 equally sized root zone environments (4 quadrants each). Each quadrant was sampled and processed for 16S amplicon, metabolomics, and X-ray computed tomography (XCT). Data download includes experimental metadata and results files for 16S rRNA sequence analysis of microbial community assembly (processed data files), liquid chromatography mass spectrometry (LC-MS) metabolomics analysis of microbial community root exudates (processed data files), X-ray computed tomography (XCT) spatial gradient analysis (raw and processed data files) of microbial community composition, and related computational modeling outputs.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Plant synthetic biology innovations for biofuels and bioproducts

Plant-based biosynthesis of fuels, chemicals, and materials promotes environmental sustainability, which includes decreases in greenhouse gas emissions, water pollution, and loss of biodiversity. Advances in plant synthetic biology (synbio) should improve precision and efficacy of genetic engineering for sustainability. Applicable synbio innovations include genome editing, gene circuit design, synthetic promoter development, gene stacking technologies, and the design of environmental sensors. Moreover, recent advancements in developing spatially resolved and single-cell omics contribute to the discovery and characterization of cell-type-specific mechanisms and spatiotemporal gene regulations in distinct plant tissues for the expression of cell- and tissue-specific genes, resulting in improved bioproduction. In conclusion, this review highlights recent plant synbio progress and new single-cell molecular profiling towards sustainable biofuel and biomaterial production.

Yang, Yongil↗
NASA NTRSDate not supplied

Neurovascular effects of simulated space radiation

A major health risk for human deep space exploration is central nervous system (CNS) damage by ionizing radiation. Simulated galactic cosmic rays or their components, especially high-linear energy transfer particles such as 56Fe ions, have been shown to cause CNS damage, neuroinflammation and cognitive dysfunction in rodent models, but their effects on human CNS remain to be investigated. CNS damage from any insult, including ionizing radiation, is partially mediated by the blood-brain barrier (BBB), which regulates interactions between CNS and the rest of the body. Astrocytes are major cellular regulators of BBB permeability and also modulate neuroinflammation and neurodegeneration. However, BBB and astrocyte functions in regulating CNS responses to space radiation remain little investigated, especially in human organ analogs. Therefore, we developed and utilized a high-throughput 3D human neurovascular organ-on-a-chip model, seeded with induced pluripotent stem cell-derived cells. The effects of time course, ionizing radiation dose and dose rate were mapped by exposing the model to either acute, high dose rate radiation with simulated galactic cosmic rays or 600 MeV/n 56Fe particles, or protracted, low dose rate gamma radiation using a 57Co sealed source setup. We investigated BBB permeability, oxidative stress, cellular damage and secreted factors over the time period between 24 hours – 2 weeks after 0.1 – 0.8 Gy irradiation. We observed that ionizing radiation exposure increased BBB permeability, caused oxidative stress, damaged endothelial cells and altered expression of inflammatory cytokines with a subset of outcomes dependent on ionizing radiation dose rate. Furthermore, our results indicated that astrocyte functions were primarily deleterious at early time points and protective later after irradiation, resembling CNS responses to injury in vivo. Our findings in organ models were complemented by studies on true spaceflight using mouse spatial and single cell multi-omics, which similarly indicated spaceflight-mediated changes in astrocyte functions. In summary, our study evaluates the regulation of neurovascular responses to simulated space radiation, suggesting astrocytes as targets for countermeasures to mitigate CNS damage in deep space exploration.

Radiation↗
DOE OSTI2025

Enhanced Spatial Proteomics and Metabolomics from a Single Tissue Section Using MALDI-MSI and LCM-microPOTS Platforms

Spatially resolved mass spectrometry (MS)-based multi-omics workflows are becoming more utilized for revealing the complex biology that occurs within tissues. However, these approaches commonly require multiple independent tissue sections to analyze the metabolite and protein compositions of these samples. This poses a significant challenge in preserving cell- or region-specific molecular fidelity, as variations between tissue sections can compromise the accurate correlation of molecular data. Here, in this study, we developed workflows for comprehensive multi-omics profiling from a single tissue section (STS) using different MS modalities. We enhanced the functionality of an electrically insulated substrate by employing metal-assisted approaches that enabled both MS-based untargeted spatial metabolomics and proteomics from STS. This allowed metabolite imaging using matrix-assisted laser desorption/ionization-MS imaging (MALDI-MSI), without compromising it for subsequent proteome profiling with laser capture microdissection (LCM)-based technology. Specifically, implementing copper tape as a backing for polyethylene naphthalate (PEN) slides enabled the detection of >140 metabolites across a poplar root tissue section using MALDI-trapped ion mobility spectrometry time of flight (timsTOF)-MS. Afterwards, we detected 6,571 unique proteins from two distinct root regions by leveraging LCM technology coupled to our microdroplet based sample preparation approach. We also developed an alternative workflow utilizing gold-coated PEN substrates for imaging with MALDI-Fourier-transform ion cyclotron resonance (FTICR)-MS, which permitted the profiling of >170 metabolites and the identification of 6,542 unique proteins across a single poplar root tissue section. These results were comparable to using each assay independently without modifications. These approaches offer new opportunities for high-resolution molecular profiling of multiple omics-levels across biological tissues.

Veličković, Marija [Pacific Northwest National Lab↗
DOE OSTI2024

Advances in mass spectrometry-enabled multiomics at single-cell resolution

We report biological organisms are multifaceted, intricate systems where slight perturbations can result in extensive changes in gene expression, protein abundance and/or activity, and metabolic flux. These changes occur at different timescales, spatially across cells of heterogeneous origins, and within single-cells. Hence, multimodal measurements at the smallest biological scales are necessary to capture dynamic changes in heterogeneous biological systems. Of the analytical techniques used to measure biomolecules, mass spectrometry (MS) has proven to be a powerful option due to its sensitivity, robustness, and flexibility with regard to the breadth of biomolecules that can be analyzed. Recently, many studies have coupled MS to other analytical techniques with the goal of measuring multiple modalities from the same single-cell. It is with these concepts in mind that we focus this review on MS-enabled multiomic measurements at single-cell or near-single- cell resolution.

47 OTHER INSTRUMENTATION↗
DOE OSTI2019

Colonies of the fungus Aspergillus niger are highly differentiated to adapt to local carbon source variation

Saprobic fungi, such as Aspergillus niger, grow as colonies consisting of a network ofbranching and fusing hyphae that are often considered to be relatively uniform entities inwhich nutrients can freely move through the hyphae. In nature, different parts of a colony areoften exposed to different nutrients. We have investigated, using a multi-omics approach,adaptation of A. niger colonies to spatially separated and compositionally different plantbiomass substrates. This demonstrated a high level of intra-colony differentiation, whichclosely matched the locally available substrate. The part of the colony exposed to pectin-richsugar beet pulp and to xylan-rich wheat bran showed high pectinolytic and high xylanolytictranscript and protein levels, respectively.This study therefore exemplifies the high ability of fungal colonies to differentiate and adaptto local conditions, ensuring efficient use of the available nutrients, rather than maintaining auniform physiology throughout the colony.

59 BASIC BIOLOGICAL SCIENCES↗