Human monocytes are divided in three major populations; classical (CD14
CD16
), non-classical (CD14
CD16
), and intermediate (CD14
CD16
). Each of these subsets is distinguished from each other by ...the expression of distinct surface markers and by their functions in homeostasis and disease. In this review, we discuss the most up-to-date phenotypic classification of human monocytes that has been greatly aided by the application of novel single-cell transcriptomic and mass cytometry technologies. Furthermore, we shed light on the role of these plastic immune cells in already recognized and emerging human chronic diseases, such as obesity, atherosclerosis, chronic obstructive pulmonary disease, lung fibrosis, lung cancer, and Alzheimer's disease. Our aim is to provide an insight into the contribution of human monocytes to the progression of these diseases and highlight their candidacy as potential therapeutic cell targets.
Blastocyst-derived stem cell lines were shown to self-organize into embryo-like structures in 3D cell culture environments. Here, we provide evidence that embryo-like structures can be generated ...solely based on transcription factor-mediated reprogramming of embryonic stem cells in a simple 3D co-culture system. Embryonic stem cells in these cultures self-organize into elongated, compartmentalized embryo-like structures reflecting aspects of the inner regions of the early post-implantation embryo. Single-cell RNA-sequencing reveals transcriptional profiles resembling epiblast, primitive-/visceral endoderm, and extraembryonic ectoderm of early murine embryos around E4.5-E5.5. In this stem cell-based embryo model, progression from rosette formation to lumenogenesis accompanied by progression from naïve- to primed pluripotency was observed within Epi-like cells. Additionally, lineage specification of primordial germ cells and distal/anterior visceral endoderm-like cells was observed in epiblast- or visceral endoderm-like compartments, respectively. The system presented in this study allows for fast and reproducible generation of embryo-like structures, providing an additional tool to study aspects of early embryogenesis.
Systemic inflammation is established as part of late-stage severe lung disease, but molecular, functional, and phenotypic changes in peripheral immune cells in early disease stages remain ill ...defined. Chronic obstructive pulmonary disease (COPD) is a major respiratory disease characterized by small-airway inflammation, emphysema, and severe breathing difficulties. Using single-cell analyses we demonstrate that blood neutrophils are already increased in early-stage COPD, and changes in molecular and functional neutrophil states correlate with lung function decline. Assessing neutrophils and their bone marrow precursors in a murine cigarette smoke exposure model identified similar molecular changes in blood neutrophils and precursor populations that also occur in the blood and lung. Our study shows that systemic molecular alterations in neutrophils and their precursors are part of early-stage COPD, a finding to be further explored for potential therapeutic targets and biomarkers for early diagnosis and patient stratification.
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•Increase in blood neutrophil molecular states in early-stage COPD•Progenitor reprogramming is linked to altered blood neutrophil states•Neutrophil state abundance correlates with lung function decline
Kapellos et al. show that systemic molecular changes in neutrophils in early-stage COPD are associated with increased granulopoiesis and demonstrate that neutrophil transcriptomic states correlate with lung function decline.
Spatially resolved omics technologies reveal context-dependent cellular regulatory networks in tissues of interest. Beyond transcriptome analysis, information on epigenetic traits and chromatin ...accessibility can provide further insights on gene regulation in health and disease. Nevertheless, compared to the enormous advancements in spatial transcriptomics technologies, the field of spatial epigenomics is much younger and still underexplored. In this study, we report laser capture microdissection coupled to ATAC-seq (LCM-ATAC-seq) applied to fresh frozen samples for the spatial characterization of chromatin accessibility. We first demonstrate the efficient use of LCM coupled to in situ tagmentation and evaluate its performance as a function of cell number, microdissected areas, and tissue type. Further, we demonstrate its use for the targeted chromatin accessibility analysis of discrete contiguous or scattered cell populations in tissues via single-nuclei capture based on immunostaining for specific cellular markers.
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•Spatially resolved chromatin accessibility profiling with LCM-ATAC-seq•Laser capture microdissection and in situ tagmentation enables targeted tissue profiling•LCM-ATAC-seq can be combined with cellular staining to investigate target populations•Not only contiguous but also scattered cell populations can be analyzed by LCM-ATAC-seq
Spatial epigenomics is still underexplored compared to the advanced evolution of spatial transcriptomics technologies. Different methods have been proposed recently, with distinct advantages and drawbacks concerning the achievable resolution, the possibility to overlay a morphological staining, and the overall applicability. In this study, we report the targeted use of LCM for the investigation of chromatin accessibility. This spatial methodology enables the analysis of scattered tissue cell populations at a mini-bulk resolution, with the possibility to integrate cellular or morphological stainings on the same processed section.
Carraro et al. establish a complete workflow for the spatial characterization of chromatin accessibility in tissues of interest based on laser capture microdissection coupled to ATAC-seq. The technology can be easily combined with a morphological staining, allowing the targeting of both contiguous and scattered cell populations with a mini-bulk resolution.
Jupiter’s changing auroral location Grodent, Denis; Gérard, Jean‐Claude; Radioti, Aikaterini ...
Journal of Geophysical Research - Space Physics,
January 2008, Letnik:
113, Številka:
A1
Journal Article, Web Resource
Recenzirano
Odprti dostop
We examine the case of significant latitudinal shifts of the Jovian northern auroral emissions appearing in a data set spanning nine years of observations with the Hubble Space Telescope in the far ...ultraviolet. The extended data set makes it possible to compare the location of the main auroral emission with similar viewing geometries and satellite positions. The main auroral emission is assumed to originate from beyond the orbit of Ganymede (15 Jovian radii). At these distances, near corotation enforcement and transfer of momentum from Jupiter to the magnetospheric plasma is ensured by means of field aligned currents. The field aligned currents away from Jupiter are carried by downward energetic electrons loosing their energy to the polar atmosphere and giving rise to the main auroral emission. Analysis of the polar projected images shows that the latitudinal location of the main emission has changed by up to 3° over long periods of time. It also shows that the footprint of Ganymede follows a similar trend. We have used the VIP4 magnetic field model to map the emission down to the equatorial plane. This mapping suggests that internal variations of the current sheet parameters might be used as an alternative or complementary explanation to the changing solar wind conditions at Jupiter to explain the observed shift of auroral latitudes.
Population-scale datasets of healthy individuals capture genetic and environmental factors influencing gene expression. The expression variance of a gene of interest (GOI) can be exploited to set up ...a quasi loss- or gain-of-function “in population” experiment. We describe here an approach, huva (human variation), taking advantage of population-scale multi-layered data to infer gene function and relationships between phenotypes and expression. Within a reference dataset, huva derives two experimental groups with LOW or HIGH expression of the GOI, enabling the subsequent comparison of their transcriptional profile and functional parameters. We demonstrate that this approach robustly identifies the phenotypic relevance of a GOI allowing the stratification of genes according to biological functions, and we generalize this concept to almost 16,000 genes in the human transcriptome. Additionally, we describe how huva predicts monocytes to be the major cell type in the pathophysiology of STAT1 mutations, evidence validated in a clinical cohort.
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•Human variation can be exploited to generate gain- or loss-of-function experiments•Huva was used to predict the function of genes central to the immune response•Transcriptome-wide huva analysis uncovers the role of STAT1 in monocytes•Huva is implemented in R as well as accessible via an easy-to-use web interface
Clinical genetics; Pathophysiology; Human genetics.
We analyze a set of 15 FUV images obtained between October 1997 and January 2001 with the Hubble Space Telescope Imaging Spectrograph (STIS), providing a good view of Saturn's south auroral oval. It ...is found that the morphology and brightness distribution of the aurora are dynamical with variations occurring on time scales of hours or less. The dayside main oval lies between 70° and 80° and is generally brighter and thinner in the morning than in the afternoon sector. The afternoon sector is characterized by more diffuse emission at higher latitudes. Weak emission is also observed poleward of the main oval up to the pole. A spot of enhanced auroral precipitation, tentatively identified as the optical signature of the dayside cusp, is sometimes observed poleward of the main oval in the noon sector, especially during periods when the morning arc is not fully developed. A spiral structure of the main oval with arcs at two latitudes in the same sector is occasionally observed. The brightness of the main oval ranges from below the STIS threshold of 1 kR of H2 emission up to ∼75 kR. The total electron precipitated power varies between 20 and 140 GW, that is, comparable to the Earth's active aurora but about two orders of magnitude less than on Jupiter. An increasing trend of the precipitated power between the 1997 and the 2000–2001 observations may be related to the rising solar activity. Six spectra of the aurora in the noon sector covering the 1200–1700 Å range are dominated by emissions of the Lyman‐α line and H2 Werner and Lyman bands. Their comparison with a synthetic model of electron excited H2 emissions indicates the presence of a weak absorption below 1400 Å by a column of methane ranging between 7 × 1015 and 2 × 1016 cm−2. The corresponding energy of the primary auroral electrons is estimated 12 ± 3 keV, using a low‐latitude model atmosphere based on Voyager occultation measurements. The main oval brightness and the characteristic electron energy are generally consistent with recent models of Saturn's aurora, which colocate the main oval with the narrow upward field‐aligned current system associated with departure from plasma corotation near the open‐closed field line boundary. The latitude of the bright morning arc is somewhat lower than model predictions based on the plasma flow velocity measured by Voyager in the middle magnetosphere.
A total of 74 images of the ultraviolet footprint of the Io flux tube (IFT) on Jupiter's upper atmosphere made with the Space Telescope Imaging Spectrograph on board the Hubble Space Telescope have ...been analyzed to characterize their location, morphology, and brightness distribution. The observations cover a wide range of central meridian Jovian longitudes and Io orbital positions and include north and south footprint emissions. Comparing the location of the IFT with that expected from the VIP4 model of the Jovian magnetic field, we find that the lead angle is generally not significantly different from zero in the System III longitude sector 125°–195°. Instead, the lead angles reach about 8° in the 50° sector, coinciding with a region of possible magnetic anomaly. We observe that the brightness of the main footprint shows intrinsic intensity changes that appear to be controlled by the system III longitude of Io and its position above or below the center of the torus. The size of the primary spot magnetically maps into a region varying from 1 to over 10 Io diameters in Io's orbital plane. Multiple footprints are observed with varying brightness relative to the mean spot. The number of spots is found to increase as Io gets closer to the torus outer edge facing the spots. The separation between the first and second spots is typically 1°–3° of longitude and increases when Io is displaced from the torus center in the direction of the IFT signature. These features confirm that Alfvén waves play an important role and generate energization of precipitated electrons. However, the observed variation of the FUV spot structure with Io's position appears inconsistent with models where reflections of Alfvén wings occur between the torus boundary and Jupiter's ionosphere. Instead, the multiple spots apparently correspond to electron precipitation generated by Alfvén waves reflected inside the plasma torus.
Reward value guides goal-directed behavior and modulates early sensory processing. Rewarding stimuli are often multisensory, but it is not known how reward value is combined across sensory ...modalities. Here we show that the integration of reward value critically depends on whether the distinct sensory inputs are perceived to emanate from the same multisensory object. We systematically manipulated the congruency in monetary reward values and the relative spatial positions of co-occurring auditory and visual stimuli that served as bimodal distractors during an oculomotor task performed by healthy human participants (male and female). The amount of interference induced by the distractors was used as an indicator of their perceptual salience. Our results across two experiments show that when reward value is linked to each modality separately, the value congruence between vision and audition determines the combined salience of the bimodal distractors. However, the reward value of vision wins over the value of audition if the two modalities are perceived to convey conflicting information regarding the spatial position of the bimodal distractors. These results show that in a task that highly relies on the processing of visual spatial information, the reward values from multiple sensory modalities are integrated with each other, each with their respective weights. This weighting depends on the strength of prior beliefs regarding a common source for incoming unisensory signals based on their congruency in reward value and perceived spatial alignment.
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