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The study of microbial diversity over time and space is fundamental to the understanding of their ecology and evolution. The underlying processes driving these patterns are not fully resolved but can be studied using population genetic approaches. Here we investigated the population genetic structure of Gonyostomum semen, a bloom-forming phytoplankton species, across two continents. The species appears to be expanding in Europe, whereas similar trends are not observed in the USA. Our aim was to investigate if populations of Gonyostomum semen in Europe and in the USA are genetically differentiated, if there is population genetic structure within the continents, and what the potential drivers of differentiation are. To this end, we used a novel method based on single-amplified genomes combined with Restriction-site Associated DNA sequencing that allows de novo genotyping of natural single-cell isolates without the need for culturing. We amplified over 900 single-cell genomes from 25 lake populations across Europe and the USA and identified two distinct population clusters, one in Europe and another in the USA. Low genetic diversity in European populations supports the hypothesized recent expansion of Gonyostomum semen on this continent. Geographic population structure within each continent was associated with differences in environmental variables that may have led to ecological divergence of population clusters. Overall, our results show that single-amplified genomes combined with Restriction-site Associated DNA sequencing can be used to analyze microalgal population structure and differentiation based on single-cell isolates from natural, uncultured samples., (© The Author(s) 2024. Published by Oxford University Press on behalf of the International Society for Microbial Ecology.)

An excessive immune response known as cytokine storm is the hallmark of severe COVID-19. The cause of this cytokine rampage is yet not known. Based on recent epidemiological evidence, we hypothesized that CD80/86 signaling is essential for this hyperinflammation, and that blocking this proinflammatory axis could be an effective therapeutic approach to protect against severe COVID-19. Here we provide exploratory evidence that abatacept, a drug that blocks CD80/86 co-stimulation, produces changes at the systemic level that are highly antagonistic of the proinflammatory processes elicited by COVID-19. Using RNA-seq from blood samples from a longitudinal cohort of n = 38 rheumatic patients treated with abatacept, we determined the immunological processes that are significantly regulated by this treatment. We then analyzed available blood RNA-seq from two COVID19 patient cohorts, a very early cohort from the epicenter of the pandemic in China (n = 3 COVID-19 cases and n = 3 controls), and a recent and larger cohort from the USA (n = 49 severe and n = 51 mild COVD-19 patients). We found a highly significant antagonism between SARS-CoV-2 infection and COVID-19 severity with the systemic response to abatacept. Analysis of previous single-cell RNA-seq data from bronchoalveolar lavage fluid from mild and severe COVID-19 patients and controls, reinforce the implication of the CD80/86 proinflammatory axis. Our functional results further support abatacept as a candidate therapeutic approach to prevent severe COVID-19.

Rationale: Lymphangioleiomyomatosis (LAM) is a metastatic neoplasm of reproductive-age women associated with mutations in tuberous sclerosis complex genes. LAM causes cystic remodeling of the lung and progressive respiratory failure. The sources and cellular characteristics of LAM cells underlying disease pathogenesis remain elusive. Objectives: Identification and characterization of LAM cells in human lung and uterus using a single-cell approach. Methods: Single-cell and single-nuclei RNA sequencing on LAM ( n  = 4) and control ( n  = 7) lungs, immunofluorescence confocal microscopy, ELISA, and aptamer proteomics were used to identify and validate LAM CORE cells and secreted biomarkers, predict cellular origins, and define molecular and cellular networks in LAM. Measurements and Main Results: A unique cell type termed LAM CORE was identified, which was distinct from, but closely related to, lung mesenchymal cells. LAM CORE cells expressing signature genes included known LAM markers such as PMEL , FIGF , CTSK , and MLANA and novel biomarkers validated by aptamer screening, ELISA, and immunofluorescence microscopy. LAM cells in lung and uterus are morphologically indistinguishable and share similar gene expression profiles and biallelic TSC2 mutations, supporting a potential uterine origin for the LAM CORE cell. Effects of LAM on resident pulmonary cell types indicated recruitment and activation of lymphatic endothelial cells. Conclusions: A unique population of LAM CORE cells was identified in lung and uterus of patients with LAM, sharing close transcriptomic identity. LAM cell selective markers, secreted biomarkers, and the predicted cellular molecular features provide new insights into the signaling and transcriptional programs that may serve as diagnostic markers and therapeutic targets to influence the pathogenesis of LAM.

Transformative technologies are enabling the construction of three-dimensional maps of tissues with unprecedented spatial and molecular resolution. Over the next seven years, the NIH Common Fund Human Biomolecular Atlas Program (HuBMAP) intends to develop a widely accessible framework for comprehensively mapping the human body at single-cell resolution by supporting technology development, data acquisition, and detailed spatial mapping. HuBMAP will integrate its efforts with other funding agencies, programs, consortia, and the biomedical research community at large towards the shared vision of a comprehensive, accessible three-dimensional molecular and cellular atlas of the human body, in health and under various disease conditions.

In systemic lupus erythematosus (SLE), type I IFNs promote induction of type I IFN-stimulated genes (ISG) and can drive B cells to produce autoantibodies. Little is known about the expression of distinct type I IFNs in lupus, particularly high-affinity IFN-β. Single-cell analyses of transitional B cells isolated from SLE patients revealed distinct B cell subpopulations, including type I IFN producers, IFN responders, and mixed IFN producer/responder clusters. Anti-Ig plus TLR3 stimulation of SLE B cells induced release of bioactive type I IFNs that could stimulate HEK-Blue cells. Increased levels of IFN-β were detected in circulating B cells from SLE patients compared with controls and were significantly higher in African American patients with renal disease and in patients with autoantibodies. Together, the results identify type I IFN-producing and -responding subpopulations within the SLE B cell compartment and suggest that some patients may benefit from specific targeting of IFN-β., (Copyright © 2018 by The American Association of Immunologists, Inc.)