The endometrium, the mucosal lining of the uterus, undergoes dynamic changes throughout the menstrual cycle in response to ovarian hormones. We have generated dense single-cell and spatial reference ...maps of the human uterus and three-dimensional endometrial organoid cultures. We dissect the signaling pathways that determine cell fate of the epithelial lineages in the lumenal and glandular microenvironments. Our benchmark of the endometrial organoids reveals the pathways and cell states regulating differentiation of the secretory and ciliated lineages both in vivo and in vitro. In vitro downregulation of WNT or NOTCH pathways increases the differentiation efficiency along the secretory and ciliated lineages, respectively. We utilize our cellular maps to deconvolute bulk data from endometrial cancers and endometriotic lesions, illuminating the cell types dominating in each of these disorders. These mechanistic insights provide a platform for future development of treatments for common conditions including endometriosis and endometrial carcinoma.
Extracellular matrix (ECM) secretion, deposition and assembly are part of a whole complex biological process influencing the microenvironment and other cellular behaviors. Emerging evidence is ...attributing a significant role to extracellular vesicles (EVs) and exosomes in a plethora of ECM-associated functions, but the role of dermal fibroblast-derived EVs in paracrine signalling is yet unclear. Herein, we investigated the effect of exosomes isolated from stimulated human dermal fibroblasts. We report that tridimensional (3D) cell culture of dermal fibroblasts promotes secretion of exosomes carrying a large quantity of proteins involved in the formation, organisation and remodelling of the ECM. In our 3D model, gene expression was highly modulated and linked to ECM, cellular migration and proliferation, as well as inflammatory response. Mass spectrometry analysis of exosomal proteins, isolated from 3D cultured fibroblast-conditioned media, revealed ECM protein enrichment, of which many were associated with the matrisome. We also show that the cytokine interleukin 6 (IL-6) is predicted to be central to the signalling pathways related to ECM formation and contributing to cell migration and proliferation. Overall, our data suggest that dermal fibroblast-derived EVs participate in many steps of the establishment of dermis's ECM.
The evaluation of protein localization changes on a systematic level is a powerful tool for understanding how cells respond to environmental, chemical, or genetic perturbations. To date, work in ...understanding these proteomic responses through high-throughput imaging has catalogued localization changes independently for each perturbation. To distinguish changes that are targeted responses to the specific perturbation or more generalized programs, we developed a scalable approach to visualize the localization behavior of proteins across multiple experiments as a quantitative pattern. By applying this approach to 24 experimental screens consisting of nearly 400,000 images, we differentiated specific responses from more generalized ones, discovered nuance in the localization behavior of stress-responsive proteins, and formed hypotheses by clustering proteins that have similar patterns. Previous approaches aim to capture all localization changes for a single screen as accurately as possible, whereas our work aims to integrate large amounts of imaging data to find unexpected new cell biology.
Data assimilation experiments of radiances from the microwave sounder SAPHIR on board the Megha‐Tropiques (MT) satellite were conducted using the global numerical weather prediction (NWP) model ...ARPEGE (Action de Recherche Petite Echelle Grande Echelle) operational at Météo‐France for the period June to August 2012. The combination of the MT's low‐inclined orbit with the SAPHIR's six channels was found to increase the number of assimilated humidity‐sensitive microwave observations in the Tropics by a factor of 3.8, compared with a control experiment using three existing Advanced Microwave Sounding Unit B and Microwave Humidity Sounder instruments. Impacts of SAPHIR on both analyses through the 4D‐Var system and forecasts are found to be positive with respect to radiosonde data and analyses by the European Centre for Medium‐range Weather Forecasts up to 12 h and neutral to positive up to 72 h. In particular, the improvement of innovation statistics for other humidity‐sensitive satellite observations when SAPHIR is assimilated indicates a positive synergy of the MT satellite with the present observing system. In addition to providing new humidity observations in the Tropics, the SAPHIR data can also be used to define new diagnostics for NWP models. In particular: (i) with the MT's orbit being non‐heliosynchronous, all local times are observed by the same sensor for a given area, which makes diurnal cycle diagnostics straightforward to set up; (ii) with SAPHIR providing more information on the vertical (six channels) than similar sensors, it can be easily used to study water‐vapour vertical structures in NWP models. The first diagnostic applied to the ARPEGE model reveals a good consistency between observed and modelled diurnal cycles in analyses over western Africa, but also reveals a 2–4 h time lag between mean observed and equivalent model brightness temperatures. The second diagnostic highlights a well‐represented vertical correlation of simulated brightness temperatures from the ARPEGE model with respect to SAPHIR over western Africa, but a too‐low vertical correlation over drier regions such as the southern Pacific Ocean during the period June to August 2012.
SARS-CoV-2 infection causing the novel coronavirus disease 2019 (COVID-19) has been responsible for more than 2.8 million deaths and nearly 125 million infections worldwide as of March 2021. In March ...2020, the World Health Organization determined that the COVID-19 outbreak is a global pandemic. The urgency and magnitude of this pandemic demanded immediate action and coordination between local, regional, national, and international actors. In that mission, researchers require access to high-quality biological materials and data from SARS-CoV-2 infected and uninfected patients, covering the spectrum of disease manifestations. The "Biobanque québécoise de la COVID-19" (BQC19) is a pan-provincial initiative undertaken in Québec, Canada to enable the collection, storage and sharing of samples and data related to the COVID-19 crisis. As a disease-oriented biobank based on high-quality biosamples and clinical data of hospitalized and non-hospitalized SARS-CoV-2 PCR positive and negative individuals. The BQC19 follows a legal and ethical management framework approved by local health authorities. The biosamples include plasma, serum, peripheral blood mononuclear cells and DNA and RNA isolated from whole blood. In addition to the clinical variables, BQC19 will provide in-depth analytical data derived from the biosamples including whole genome and transcriptome sequencing, proteome and metabolome analyses, multiplex measurements of key circulating markers as well as anti-SARS-CoV-2 antibody responses. BQC19 will provide the scientific and medical communities access to data and samples to better understand, manage and ultimately limit, the impact of COVID-19. In this paper we present BQC19, describe the process according to which it is governed and organized, and address opportunities for future research collaborations. BQC19 aims to be a part of a global communal effort addressing the challenges of COVID-19.
Climate change affects global agricultural production and threatens food security. Faster phenological development of crops due to climate warming is one of the main drivers for potential future ...yield reductions. To counter the effect of faster maturity, adapted varieties would require more heat units to regain the previous growing period length. In this study, we investigate the effects of variety adaptation on global caloric production under four different future climate change scenarios for maize, rice, soybean, and wheat. Thereby, we empirically identify areas that could require new varieties and areas where variety adaptation could be achieved by shifting existing varieties into new regions. The study uses an ensemble of seven global gridded crop models and five CMIP6 climate models. We found that 39% (SSP5‐8.5) of global cropland could require new crop varieties to avoid yield loss from climate change by the end of the century. At low levels of warming (SSP1‐2.6), 85% of currently cultivated land can draw from existing varieties to shift within an agro‐ecological zone for adaptation. The assumptions on available varieties for adaptation have major impacts on the effectiveness of variety adaptation, which could more than half in SSP5‐8.5. The results highlight that region‐specific breeding efforts are required to allow for a successful adaptation to climate change.
Variety adaptation could potentially outweigh climate change induced production losses and increase global production by 19%. Therefore, new adapted crop varieties are required. In 2100, about 40% of global cropland could require new adapted crop varieties to avoid yield losses from climate change. However, under high level of warming, the risk increases that adapted crop varieties are not available, because regional temperatures could exceed temperature ranges of currently grown cultivars. Thus, regional breeding efforts are required to face the challenge.
We review observational, experimental, and model results on how plants respond to extreme climatic conditions induced by changing climatic variability. Distinguishing between impacts of changing mean ...climatic conditions and changing climatic variability on terrestrial ecosystems is generally underrated in current studies. The goals of our review are thus (1) to identify plant processes that are vulnerable to changes in the variability of climatic variables rather than to changes in their mean, and (2) to depict/evaluate available study designs to quantify responses of plants to changing climatic variability. We find that phenology is largely affected by changing mean climate but also that impacts of climatic variability are much less studied, although potentially damaging. We note that plant water relations seem to be very vulnerable to extremes driven by changes in temperature and precipitation and that heatwaves and flooding have stronger impacts on physiological processes than changing mean climate. Moreover, interacting phenological and physiological processes are likely to further complicate plant responses to changing climatic variability. Phenological and physiological processes and their interactions culminate in even more sophisticated responses to changing mean climate and climatic variability at the species and community level. Generally, observational studies are well suited to study plant responses to changing mean climate, but less suitable to gain a mechanistic understanding of plant responses to climatic variability. Experiments seem best suited to simulate extreme events. In models, temporal resolution and model structure are crucial to capture plant responses to changing climatic variability. We highlight that a combination of experimental, observational, and/or modeling studies have the potential to overcome important caveats of the respective individual approaches.
Arctic ecosystems are particularly vulnerable to climate change because of Arctic amplification. Here, we assessed the climatic impacts of low-end, 1.5 °C, and 2.0 °C global temperature increases ...above pre-industrial levels, on the warming of terrestrial ecosystems in northern high latitudes (NHL, above 60 °N including pan-Arctic tundra and boreal forests) under the framework of the Inter-Sectoral Impact Model Intercomparison Project phase 2b protocol. We analyzed the simulated changes of net primary productivity, vegetation biomass, and soil carbon stocks of eight ecosystem models that were forced by the projections of four global climate models and two atmospheric greenhouse gas pathways (RCP2.6 and RCP6.0). Our results showed that considerable impacts on ecosystem carbon budgets, particularly primary productivity and vegetation biomass, are very likely to occur in the NHL areas. The models agreed on increases in primary productivity and biomass accumulation, despite considerable inter-model and inter-scenario differences in the magnitudes of the responses. The inter-model variability highlighted the inadequacies of the present models, which fail to consider important components such as permafrost and wildfire. The simulated impacts were attributable primarily to the rapid temperature increases in the NHL and the greater sensitivity of northern vegetation to warming, which contrasted with the less pronounced responses of soil carbon stocks. The simulated increases of vegetation biomass by 30-60 Pg C in this century have implications for climate policy such as the Paris Agreement. Comparison between the results at two warming levels showed the effectiveness of emission reductions in ameliorating the impacts and revealed unavoidable impacts for which adaptation options are urgently needed in the NHL ecosystems.
The sesquiterpenoid abscisic acid (ABA) mediates an assortment of responses across a variety of kingdoms including both higher plants and animals. In plants, where most is known, a linear core ABA ...signaling pathway has been identified. However, the complexity of ABA-dependent gene expression suggests that ABA functions through an intricate network. Here, using systems biology approaches that focused on genes transcriptionally regulated by ABA, we defined an ABA signaling network of over 500 interactions among 138 proteins. This map greatly expanded ABA core signaling but was still manageable for systematic analysis. For example, functional analysis was used to identify an ABA module centered on two sucrose nonfermenting (SNF)-like kinases. We also used coexpression analysis of interacting partners within the network to uncover dynamic subnetwork structures in response to different abiotic stresses. This comprehensive ABA resource allows for application of approaches to understanding ABA functions in higher plants.
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•High-quality ABA network encompassing 500 interactions among 138 proteins•Doubled the number of proteins that interact with core ABA signaling components•Identified an SNRK3 signaling module that attenuates early ABA responses•Mapping coexpression predicted the function of genes under abiotic stresses
Lumba et al. define a focused ABA signaling network of over 500 interactions among 138 proteins. The network can be queried functionally to define genes involved in ABA signaling. When merged with global expression patterns centered on abiotic stresses, the ABA network reveals specific modules related to each stress condition.
Terrestrial gross primary productivity (GPP) is the largest component of the global carbon cycle and a key process for understanding land ecosystems dynamics. In this study, we used GPP estimates ...from a combination of eight global biome models participating in the Inter-Sectoral Impact-Model Intercomparison Project phase 2a (ISIMIP2a), the Moderate Resolution Spectroradiometer (MODIS) GPP product, and a data-driven product (Model Tree Ensemble, MTE) to study the spatiotemporal variability of GPP at the regional and global levels. We found the 2000-2010 total global GPP estimated from the model ensemble to be 117 ± 13 Pg C yr−1 (mean ± 1 standard deviation), which was higher than MODIS (112 Pg C yr−1), and close to the MTE (120 Pg C yr−1). The spatial patterns of MODIS, MTE and ISIMIP2a GPP generally agree well, but their temporal trends are different, and the seasonality and inter-annual variability of GPP at the regional and global levels are not completely consistent. For the model ensemble, Tropical Latin America contributes the most to global GPP, Asian regions contribute the most to the global GPP trend, the Northern Hemisphere regions dominate the global GPP seasonal variations, and Oceania is likely the largest contributor to inter-annual variability of global GPP. However, we observed large uncertainties across the eight ISIMIP2a models, which are probably due to the differences in the formulation of underlying photosynthetic processes. The results of this study are useful in understanding the contributions of different regions to global GPP and its spatiotemporal variability, how the model- and observational-based GPP estimates differ from each other in time and space, and the relative strength of the eight models. Our results also highlight the models' ability to capture the seasonality of GPP that are essential for understanding the inter-annual and seasonal variability of GPP as a major component of the carbon cycle.
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