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1.
Nat Commun ; 15(1): 6158, 2024 Jul 22.
Article in English | MEDLINE | ID: mdl-39039045

ABSTRACT

Common and rare alleles are now being annotated across millions of human genomes, and omics technologies are increasingly being used to develop health and treatment recommendations. However, these alleles have not yet been systematically characterized relative to aerospace medicine. Here, we review published alleles naturally found in human cohorts that have a likely protective effect, which is linked to decreased cancer risk and improved bone, muscular, and cardiovascular health. Although some technical and ethical challenges remain, research into these protective mechanisms could translate into improved nutrition, exercise, and health recommendations for crew members during deep space missions.


Subject(s)
Alleles , Precision Medicine , Space Flight , Humans , Precision Medicine/methods , Aerospace Medicine , Genome, Human , Neoplasms/genetics , Neoplasms/therapy
2.
Nature ; 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38862027

ABSTRACT

The recent acceleration of commercial, private, and multi-national spaceflight has created an unprecedented level of activity in low Earth orbit (LEO), concomitant with the highest-ever number of crewed missions entering space and preparations for exploration-class (>1 year) missions. Such rapid advancement into space from many new companies, countries, and space-related entities has enabled a"Second Space Age." This new era is also poised to leverage, for the first time, modern tools and methods of molecular biology and precision medicine, thus enabling precision aerospace medicine for the crews. The applications of these biomedical technologies and algorithms are diverse, encompassing multi-omic, single-cell, and spatial biology tools to investigate human and microbial responses to spaceflight. Additionally, they extend to the development of new imaging techniques, real-time cognitive assessments, physiological monitoring, and personalized risk profiles tailored for astronauts. Furthermore, these technologies enable advancements in pharmacogenomics (PGx), as well as the identification of novel spaceflight biomarkers and the development of corresponding countermeasures. In this review, we highlight some of the recent biomedical research from the National Aeronautics and Space Administration (NASA), Japan Aerospace Exploration Agency (JAXA), European Space Agency (ESA), and other space agencies, and also detail the commercial spaceflight sector's (e.g. SpaceX, Blue Origin, Axiom, Sierra Space) entrance into aerospace medicine and space biology, the first aerospace medicine biobank, and the myriad upcoming missions that will utilize these tools to ensure a permanent human presence beyond LEO, venturing out to other planets and moons.

3.
Nat Commun ; 15(1): 4778, 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38862479

ABSTRACT

Impairment of the central nervous system (CNS) poses a significant health risk for astronauts during long-duration space missions. In this study, we employed an innovative approach by integrating single-cell multiomics (transcriptomics and chromatin accessibility) with spatial transcriptomics to elucidate the impact of spaceflight on the mouse brain in female mice. Our comparative analysis between ground control and spaceflight-exposed animals revealed significant alterations in essential brain processes including neurogenesis, synaptogenesis and synaptic transmission, particularly affecting the cortex, hippocampus, striatum and neuroendocrine structures. Additionally, we observed astrocyte activation and signs of immune dysfunction. At the pathway level, some spaceflight-induced changes in the brain exhibit similarities with neurodegenerative disorders, marked by oxidative stress and protein misfolding. Our integrated spatial multiomics approach serves as a stepping stone towards understanding spaceflight-induced CNS impairments at the level of individual brain regions and cell types, and provides a basis for comparison in future spaceflight studies. For broader scientific impact, all datasets from this study are available through an interactive data portal, as well as the National Aeronautics and Space Administration (NASA) Open Science Data Repository (OSDR).


Subject(s)
Brain , Neurons , Space Flight , Animals , Mice , Female , Brain/metabolism , Brain/pathology , Neurons/metabolism , Transcriptome , Neurogenesis , Single-Cell Analysis , Mice, Inbred C57BL , Synaptic Transmission , Weightlessness/adverse effects , Astrocytes/metabolism , Oxidative Stress , Gene Expression Profiling , Multiomics
4.
Nat Commun ; 15(1): 4952, 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38862505

ABSTRACT

Future multi-year crewed planetary missions will motivate advances in aerospace nutrition and telehealth. On Earth, the Human Cell Atlas project aims to spatially map all cell types in the human body. Here, we propose that a parallel Human Cell Space Atlas could serve as an openly available, global resource for space life science research. As humanity becomes increasingly spacefaring, high-resolution omics on orbit could permit an advent of precision spaceflight healthcare. Alongside the scientific potential, we consider the complex ethical, cultural, and legal challenges intrinsic to the human space omics discipline, and how philosophical frameworks may benefit from international perspectives.


Subject(s)
Astronauts , Space Flight , Humans , Genomics/methods , Human Body
5.
Plant Cell ; 36(4): 812-828, 2024 Mar 29.
Article in English | MEDLINE | ID: mdl-38231860

ABSTRACT

Single-cell and single-nucleus RNA-sequencing technologies capture the expression of plant genes at an unprecedented resolution. Therefore, these technologies are gaining traction in plant molecular and developmental biology for elucidating the transcriptional changes across cell types in a specific tissue or organ, upon treatments, in response to biotic and abiotic stresses, or between genotypes. Despite the rapidly accelerating use of these technologies, collective and standardized experimental and analytical procedures to support the acquisition of high-quality data sets are still missing. In this commentary, we discuss common challenges associated with the use of single-cell transcriptomics in plants and propose general guidelines to improve reproducibility, quality, comparability, and interpretation and to make the data readily available to the community in this fast-developing field of research.


Subject(s)
Gene Expression Profiling , Plants , Reproducibility of Results , Plants/genetics , Stress, Physiological/genetics , Information Storage and Retrieval
6.
PLoS One ; 19(1): e0296672, 2024.
Article in English | MEDLINE | ID: mdl-38241213

ABSTRACT

Single-cell transcriptomics has the potential to provide novel insights into poorly studied microbial eukaryotes. Although several such technologies are available and benchmarked on mammalian cells, few have been tested on protists. Here, we applied a microarray single-cell sequencing (MASC-seq) technology, that generates microscope images of cells in parallel with capturing their transcriptomes, on three species representing important plankton groups with different cell structures; the ciliate Tetrahymena thermophila, the diatom Phaeodactylum tricornutum, and the dinoflagellate Heterocapsa sp. Both the cell fixation and permeabilization steps were adjusted. For the ciliate and dinoflagellate, the number of transcripts of microarray spots with single cells were significantly higher than for background spots, and the overall expression patterns were correlated with that of bulk RNA, while for the much smaller diatom cells, it was not possible to separate single-cell transcripts from background. The MASC-seq method holds promise for investigating "microbial dark matter", although further optimizations are necessary to increase the signal-to-noise ratio.


Subject(s)
Gene Expression Profiling , Plankton , Animals , Plankton/genetics , Gene Expression Profiling/methods , Transcriptome , Eukaryota , RNA , Mammals
7.
Nat Biotechnol ; 2023 Nov 20.
Article in English | MEDLINE | ID: mdl-37985875

ABSTRACT

The interactions of microorganisms among themselves and with their multicellular host take place at the microscale, forming complex networks and spatial patterns. Existing technology does not allow the simultaneous investigation of spatial interactions between a host and the multitude of its colonizing microorganisms, which limits our understanding of host-microorganism interactions within a plant or animal tissue. Here we present spatial metatranscriptomics (SmT), a sequencing-based approach that leverages 16S/18S/ITS/poly-d(T) multimodal arrays for simultaneous host transcriptome- and microbiome-wide characterization of tissues at 55-µm resolution. We showcase SmT in outdoor-grown Arabidopsis thaliana leaves as a model system, and find tissue-scale bacterial and fungal hotspots. By network analysis, we study inter- and intrakingdom spatial interactions among microorganisms, as well as the host response to microbial hotspots. SmT provides an approach for answering fundamental questions on host-microbiome interplay.

8.
Genome Biol ; 24(1): 237, 2023 10 19.
Article in English | MEDLINE | ID: mdl-37858234

ABSTRACT

Technologies to study localized host-pathogen interactions are urgently needed. Here, we present a spatial transcriptomics approach to simultaneously capture host and pathogen transcriptome-wide spatial gene expression information from human formalin-fixed paraffin-embedded (FFPE) tissue sections at a near single-cell resolution. We demonstrate this methodology in lung samples from COVID-19 patients and validate our spatial detection of SARS-CoV-2 against RNAScope and in situ sequencing. Host-pathogen colocalization analysis identified putative modulators of SARS-CoV-2 infection in human lung cells. Our approach provides new insights into host response to pathogen infection through the simultaneous, unbiased detection of two transcriptomes in FFPE samples.


Subject(s)
COVID-19 , Transcriptome , Humans , Tissue Fixation , Formaldehyde , SARS-CoV-2
9.
Nat Commun ; 14(1): 6500, 2023 10 14.
Article in English | MEDLINE | ID: mdl-37838705

ABSTRACT

Several important human infectious diseases are caused by microscale-sized parasitic nematodes like filarial worms. Filarial worms have their own spatial tissue organization; to uncover this tissue structure, we need methods that can spatially resolve these miniature specimens. Most filarial worms evolved a mutualistic association with endosymbiotic bacteria Wolbachia. However, the mechanisms underlying the dependency of filarial worms on the fitness of these bacteria remain unknown. As Wolbachia is essential for the development, reproduction, and survival of filarial worms, we spatially explored how Wolbachia interacts with the worm's reproductive system by performing a spatial characterization using Spatial Transcriptomics (ST) across a posterior region containing reproductive tissue and developing embryos of adult female Brugia malayi worms. We provide a proof-of-concept for miniature-ST to explore spatial gene expression patterns in small sample types, demonstrating the method's ability to uncover nuanced tissue region expression patterns, observe the spatial localization of key B. malayi - Wolbachia pathway genes, and co-localize the B. malayi spatial transcriptome in Wolbachia tissue regions, also under antibiotic treatment. We envision our approach will open up new avenues for the study of infectious diseases caused by micro-scale parasitic worms.


Subject(s)
Communicable Diseases , Parasites , Wolbachia , Animals , Female , Humans , Parasites/genetics , Transcriptome , Anti-Bacterial Agents/metabolism , Gene Expression Profiling , Wolbachia/genetics , Wolbachia/metabolism , Symbiosis/genetics
10.
iScience ; 26(9): 107289, 2023 Sep 15.
Article in English | MEDLINE | ID: mdl-37636054

ABSTRACT

Following on from the NASA twins' study, there has been a tremendous interest in the use of omics techniques in spaceflight. Individual space agencies, NASA's GeneLab, JAXA's ibSLS, and the ESA-funded Space Omics Topical Team and the International Standards for Space Omics Processing (ISSOP) groups have established several initiatives to support this growth. Here, we present recommendations from the Space Omics Topical Team to promote standard application of space omics in Europe. We focus on four main themes: i) continued participation in and coordination with international omics endeavors, ii) strengthening of the European space omics infrastructure including workforce and facilities, iii) capitalizing on the emerging opportunities in the commercial space sector, and iv) capitalizing on the emerging opportunities in human subjects research.

11.
iScience ; 26(1): 105857, 2023 Jan 20.
Article in English | MEDLINE | ID: mdl-36624836

ABSTRACT

Cardiomyocytes play key roles during cardiogenesis, but have poorly understood features, especially in prenatal stages. Here, we characterized human prenatal cardiomyocytes, 6.5-7 weeks post-conception, by integrating single-cell RNA sequencing, spatial transcriptomics, and ligand-receptor interaction information. Using a computational workflow developed to dissect cell type heterogeneity, localize cell types, and explore their molecular interactions, we identified eight types of developing cardiomyocyte, more than double compared to the ones identified in the Human Developmental Cell Atlas. These have high variability in cell cycle activity, mitochondrial content, and connexin gene expression, and are differentially distributed in the ventricles, including outflow tract, and atria, including sinoatrial node. Moreover, cardiomyocyte ligand-receptor crosstalk is mainly with non-cardiomyocyte cell types, encompassing cardiogenesis-related pathways. Thus, early prenatal human cardiomyocytes are highly heterogeneous and develop unique location-dependent properties, with complex ligand-receptor crosstalk. Further elucidation of their developmental dynamics may give rise to new therapies.

12.
Cell Rep Methods ; 2(11): 100325, 2022 11 21.
Article in English | MEDLINE | ID: mdl-36452864

ABSTRACT

Single-cell RNA sequencing (scRNA-seq) and spatially resolved transcriptomics (SRT) have experienced rapid development in recent years. The findings of spaceflight-based scRNA-seq and SRT investigations are likely to improve our understanding of life in space and our comprehension of gene expression in various cell systems and tissue dynamics. However, compared to their Earth-based counterparts, gene expression experiments conducted in spaceflight have not experienced the same pace of development. Out of the hundreds of spaceflight gene expression datasets available, only a few used scRNA-seq and SRT. In this perspective piece, we explore the growing importance of scRNA-seq and SRT in space biology and discuss the challenges and considerations relevant to robust experimental design to enable growth of these methods in the field.


Subject(s)
Space Flight , Transcriptome , Transcriptome/genetics , Sequence Analysis, RNA/methods , Single-Cell Analysis/methods , Gene Expression Profiling/methods
13.
Patterns (N Y) ; 3(10): 100550, 2022 Oct 14.
Article in English | MEDLINE | ID: mdl-36277820

ABSTRACT

Widespread generation and analysis of omics data have revolutionized molecular medicine on Earth, yet its power to yield new mechanistic insights and improve occupational health during spaceflight is still to be fully realized in humans. Nevertheless, rapid technological advancements and ever-regular spaceflight programs mean that longitudinal, standardized, and cost-effective collection of human space omics data are firmly within reach. Here, we consider the practicality and scientific return of different sampling methods and omic types in the context of human spaceflight. We also appraise ethical and legal considerations pertinent to omics data derived from European astronauts and spaceflight participants (SFPs). Ultimately, we propose that a routine omics collection program in spaceflight and analog environments presents a golden opportunity. Unlocking this bright future of artificial intelligence (AI)-driven analyses and personalized medicine approaches will require further investigation into best practices, including policy design and standardization of omics data, metadata, and sampling methods.

14.
iScience ; 25(9): 104868, 2022 Sep 16.
Article in English | MEDLINE | ID: mdl-36060057

ABSTRACT

In a broadening and more competitive space exploration landscape, playing at scale is necessary to obtain results. European researchers share their lessons learned on growing a research program where omics techniques can feed new knowledge, both fundamental and practical, for space exploration. Sending people to new space destinations will require interdisciplinary research centered around omics and personalized medicine, with added constraints of low-gravity and high-radiation environments.

15.
Heliyon ; 8(6): e09651, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35756107

ABSTRACT

Spatial information of tissues is an essential component to reach a holistic overview of gene expression mechanisms. The sequencing-based Spatial transcriptomics approach allows to spatially barcode the whole transcriptome of tissue sections using microarray glass slides. However, manual preparation of high-quality tissue sequencing libraries is time-consuming and subjected to technical variability. Here, we present an automated adaptation of the 10x Genomics Visium library construction on the widely used Agilent Bravo Liquid Handling Platform. Compared to the manual Visium library preparation, our automated approach reduces hands-on time by over 80% and provides higher throughput and robustness. Our automated Visium library preparation protocol provides a new strategy to standardize spatially resolved transcriptomics analysis of tissues at scale.

16.
Cell ; 185(1): 204-217.e14, 2022 01 06.
Article in English | MEDLINE | ID: mdl-34965378

ABSTRACT

Conifers dominate the world's forest ecosystems and are the most widely planted tree species. Their giant and complex genomes present great challenges for assembling a complete reference genome for evolutionary and genomic studies. We present a 25.4-Gb chromosome-level assembly of Chinese pine (Pinus tabuliformis) and revealed that its genome size is mostly attributable to huge intergenic regions and long introns with high transposable element (TE) content. Large genes with long introns exhibited higher expressions levels. Despite a lack of recent whole-genome duplication, 91.2% of genes were duplicated through dispersed duplication, and expanded gene families are mainly related to stress responses, which may underpin conifers' adaptation, particularly in cold and/or arid conditions. The reproductive regulation network is distinct compared with angiosperms. Slow removal of TEs with high-level methylation may have contributed to genomic expansion. This study provides insights into conifer evolution and resources for advancing research on conifer adaptation and development.


Subject(s)
Epigenome , Evolution, Molecular , Gene Expression Regulation, Plant , Genes, Plant , Pinus/genetics , Acclimatization/genetics , Chromosomes, Plant/genetics , Cycadopsida/genetics , DNA Transposable Elements/genetics , Forests , Gene Regulatory Networks , Genome Size , Genomics/methods , Introns , Magnoliopsida/genetics
17.
Sci Rep ; 11(1): 18408, 2021 09 15.
Article in English | MEDLINE | ID: mdl-34526620

ABSTRACT

Purkinje cells are critically involved in processing the cerebellar functions by shaping and coordinating commands that they receive. Here, we demonstrate experimentally that in the adult zebrafish valvular part of the cerebellum, the Purkinje cells exhibited variable firing and functional responses and allowed the categorization into three firing classes. Compared with the Purkinje cells in the corpus cerebelli, the valvular Purkinje cells receive weak and occasional input from the inferior olive and are not active during locomotion. Together, our findings expand further the regional functional differences of the Purkinje cell population and expose their non-locomotor functionality.


Subject(s)
Cerebellum/cytology , Cerebellum/physiology , Purkinje Cells/cytology , Zebrafish/physiology , Animals , Animals, Genetically Modified , Biomarkers , Cerebellum/metabolism , Electrophysiological Phenomena , Fluorescent Antibody Technique , Gene Expression , Genes, Reporter , Immunohistochemistry , Purkinje Cells/metabolism
18.
Elife ; 102021 09 07.
Article in English | MEDLINE | ID: mdl-34491200

ABSTRACT

With growing populations and pressing environmental problems, future economies will be increasingly plant-based. Now is the time to reimagine plant science as a critical component of fundamental science, agriculture, environmental stewardship, energy, technology and healthcare. This effort requires a conceptual and technological framework to identify and map all cell types, and to comprehensively annotate the localization and organization of molecules at cellular and tissue levels. This framework, called the Plant Cell Atlas (PCA), will be critical for understanding and engineering plant development, physiology and environmental responses. A workshop was convened to discuss the purpose and utility of such an initiative, resulting in a roadmap that acknowledges the current knowledge gaps and technical challenges, and underscores how the PCA initiative can help to overcome them.


Subject(s)
Plant Cells , Agriculture , Chlamydomonas reinhardtii , Chloroplasts , Computational Biology , Image Processing, Computer-Assisted , Plant Cells/physiology , Plant Development , Plants/classification , Plants/genetics , Zea mays
19.
Mar Biotechnol (NY) ; 23(3): 402-416, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33931810

ABSTRACT

Barnacles are key marine crustaceans in several habitats, and they constitute a common practical problem by causing biofouling on man-made marine constructions and ships. Despite causing considerable ecological and economic impacts, there is a surprising void of basic genomic knowledge, and a barnacle reference genome is lacking. We here set out to characterize the genome of the bay barnacle Balanus improvisus (= Amphibalanus improvisus) based on short-read whole-genome sequencing and experimental genome size estimation. We show both experimentally (DNA staining and flow cytometry) and computationally (k-mer analysis) that B. improvisus has a haploid genome size of ~ 740 Mbp. A pilot genome assembly rendered a total assembly size of ~ 600 Mbp and was highly fragmented with an N50 of only 2.2 kbp. Further assembly-based and assembly-free analyses revealed that the very limited assembly contiguity is due to the B. improvisus genome having an extremely high nucleotide diversity (π) in coding regions (average π ≈ 5% and average π in fourfold degenerate sites ≈ 20%), and an overall high repeat content (at least 40%). We also report on high variation in the α-octopamine receptor OctA (average π = 3.6%), which might increase the risk that barnacle populations evolve resistance toward antifouling agents. The genomic features described here can help in planning for a future high-quality reference genome, which is urgently needed to properly explore and understand proteins of interest in barnacle biology and marine biotechnology and for developing better antifouling strategies.


Subject(s)
Genome , Thoracica/genetics , Animals , Biofouling , Nucleotides , Receptors, Biogenic Amine/genetics
20.
Curr Opin Plant Biol ; 60: 102041, 2021 04.
Article in English | MEDLINE | ID: mdl-33915520

ABSTRACT

To achieve a complete understanding of how organisms function, there is a need to study their fundamental unit, the cell, in its spatial context. In recent years, we have seen fast-paced technological progress to study the transcriptional content of single cells and their spatial relationships. This review highlights modern advancements in single-cell RNA-sequencing, provides an overview of the technologies that led the plant field toward spatial transcriptomics, and describes the available spatial transcriptomics approaches providing examples of their application to plant tissues. In addition, it discusses the integration of these methods to study plant tissues. Taken together, we propose a central role of spatial transcriptomics approaches in plant science.


Subject(s)
Single-Cell Analysis , Transcriptome , Computational Biology , Plants/genetics , Sequence Analysis, RNA , Transcriptome/genetics
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