Mutations in
-a gene encoding the cystine transporter cystinosin-cause the rare, autosomal, recessive, lysosomal-storage disease cystinosis. Research has also implicated cystinosin in modulating the ...mTORC1 pathway, which serves as a core regulator of cellular metabolism, proliferation, survival, and autophagy. In its severest form, cystinosis is characterized by cystine accumulation, renal proximal tubule dysfunction, and kidney failure. Because treatment with the cystine-depleting drug cysteamine only slows disease progression, there is an urgent need for better treatments.
To address a lack of good human-based cell culture models for studying cystinosis, we generated the first human induced pluripotent stem cell (iPSC) and kidney organoid models of the disorder. We used a variety of techniques to examine hallmarks of cystinosis-including cystine accumulation, lysosome size, the autophagy pathway, and apoptosis-and performed RNA sequencing on isogenic lines to identify differentially expressed genes in the cystinosis models compared with controls.
Compared with controls, these cystinosis models exhibit elevated cystine levels, increased apoptosis, and defective basal autophagy. Cysteamine treatment ameliorates this phenotype, except for abnormalities in apoptosis and basal autophagy. We found that treatment with everolimus, an inhibitor of the mTOR pathway, reduces the number of large lysosomes, decreases apoptosis, and activates autophagy, but it does not rescue the defect in cystine loading. However, dual treatment of cystinotic iPSCs or kidney organoids with cysteamine and everolimus corrects all of the observed phenotypic abnormalities.
These observations suggest that combination therapy with a cystine-depleting drug such as cysteamine and an mTOR pathway inhibitor such as everolimus has potential to improve treatment of cystinosis.
Kidney organoids made from pluripotent stem cells have the potential to revolutionize how kidney development, disease, and injury are studied. Current protocols are technically complex, suffer from ...poor reproducibility, and have high reagent costs that restrict scalability. To overcome some of these issues, we have established a simple, inexpensive, and robust method to grow kidney organoids in bulk from human induced pluripotent stem cells. Our organoids develop tubular structures by day 8 and show optimal tissue morphology at day 14. A comparison with fetal human kidneys suggests that day-14 organoid tissue most closely resembles late capillary loop stage nephrons. We show that deletion of HNF1B, a transcription factor linked to congenital kidney defects, interferes with tubulogenesis, validating our experimental system for studying renal developmental biology. Taken together, our protocol provides a fast, efficient, and cost-effective method for generating large quantities of human fetal kidney tissue, enabling the study of normal and aberrant kidney development.
Display omitted
•Technically simple and cost-efficient protocol for kidney organoid generation•Tubular organoids are obtained rapidly, with high efficiency, yield, and robustness•Organoids contain nephrons that correspond to human fetal nephrons•The applicability to model congenital kidney defects is presented
In this study, Przepiorski et al. present a technically simple and robust protocol to derive kidney organoids from human induced pluripotent stem cells. This technique is inexpensive and efficient, allowing kidney organoids to be generated in bulk. Organoids are obtained rapidly (within 8 days) and, based on their segmentation pattern, correspond to “late capillary loop” stage fetal human nephrons.
Abstract
Arctic shrub expansion alters carbon budgets, albedo, and warming rates in high latitudes but remains challenging to predict due to unclear underlying controls. Observational studies and ...models typically use relationships between observed shrub presence and current environmental suitability (bioclimate and topography) to predict shrub expansion, while omitting shrub demographic processes and non-stationary response to changing climate. Here, we use high-resolution satellite imagery across Alaska and western Canada to show that observed shrub expansion has not been controlled by environmental suitability during 1984–2014, but can only be explained by considering seed dispersal and fire. These findings provide the impetus for better observations of recruitment and for incorporating currently underrepresented processes of seed dispersal and fire in land models to project shrub expansion and climate feedbacks. Integrating these dynamic processes with projected fire extent and climate, we estimate shrubs will expand into 25% of the non-shrub tundra by 2100, in contrast to 39% predicted based on increasing environmental suitability alone. Thus, using environmental suitability alone likely overestimates and misrepresents shrub expansion pattern and its associated carbon sink.
Numerous current efforts seek to improve the representation of ecosystem ecology and vegetation demographic processes within Earth System Models (ESMs). These developments are widely viewed as an ...important step in developing greater realism in predictions of future ecosystem states and fluxes. Increased realism, however, leads to increased model complexity, with new features raising a suite of ecological questions that require empirical constraints. Here, we review the developments that permit the representation of plant demographics in ESMs, and identify issues raised by these developments that highlight important gaps in ecological understanding. These issues inevitably translate into uncertainty in model projections but also allow models to be applied to new processes and questions concerning the dynamics of real‐world ecosystems. We argue that stronger and more innovative connections to data, across the range of scales considered, are required to address these gaps in understanding. The development of first‐generation land surface models as a unifying framework for ecophysiological understanding stimulated much research into plant physiological traits and gas exchange. Constraining predictions at ecologically relevant spatial and temporal scales will require a similar investment of effort and intensified inter‐disciplinary communication.
In this review, we summarize in detail the development of vegetation demographics models as components of Earth System Models. We particularly highlight the ecological uncertainties around the strength of growth‐resource acquisition feedbacks that are common across model developments, and illustrate the myriad new opportunities for ecological‐scale data streams to inform and validate these new model structures.
Tropical forests absorb large amounts of atmospheric CO2 through photosynthesis but elevated temperatures suppress this absorption and promote monoterpene emissions. Using 13CO2 labeling, here we ...show that monoterpene emissions from tropical leaves derive from recent photosynthesis and demonstrate distinct temperature optima for five groups (Groups 1–5), potentially corresponding to different enzymatic temperature‐dependent reaction mechanisms within β‐ocimene synthases. As diurnal and seasonal leaf temperatures increased during the Amazonian 2015 El Niño event, leaf and landscape monoterpene emissions showed strong linear enrichments of β‐ocimenes (+4.4% °C−1) at the expense of other monoterpene isomers. The observed inverse temperature response of α‐pinene (−0.8% °C−1), typically assumed to be the dominant monoterpene with moderate reactivity, was not accurately simulated by current global emission models. Given that β‐ocimenes are highly reactive with respect to both atmospheric and biological oxidants, the results suggest that highly reactive β‐ocimenes may play important roles in the thermotolerance of photosynthesis by functioning as effective antioxidants within plants and as efficient atmospheric precursors of secondary organic aerosols. Thus, monoterpene composition may represent a new sensitive ‘thermometer’ of leaf oxidative stress and atmospheric reactivity, and therefore a new tool in future studies of warming impacts on tropical biosphere‐atmosphere carbon‐cycle feedbacks.
High temperatures threaten the ability of tropical forests to absorb large amounts of atmospheric CO2 by photosynthesis, but promote the emissions of monoterpenes (C10H16). Here, we show that as record high leaf diurnal and seasonal temperatures were experienced in the central Amazon during the 2015 El Niño event, leaf and landscape monoterpene emissions showed strong linear enrichments of β‐ocimenes (+4.4% °C−1) at the expense of other monoterpene isomers. The results demonstrate consistent temperature sensitivities of five monoterpene groups that were reproducible across large temporal (minutes to seasons) and spatial (leaves to landscape) scales but are not accurately simulated in current Earth Systems models. We suggest that the shift to highly reactive β‐ocimenes (Group 1) at high leaf temperatures facilitates forest‐atmosphere response to warming by functioning as: (1) effective antioxidants in plants, enhancing thermotolerance of photosynthesis and (2) as efficient atmospheric precursors of secondary organic aerosols, enhancing cloud cover and precipitation.
Tree mortality is a key driver of forest community composition and carbon dynamics. Strong winds associated with severe convective storms are dominant natural drivers of tree mortality in the Amazon. ...Why forests vary with respect to their vulnerability to wind events and how the predicted increase in storm events might affect forest ecosystems within the Amazon are not well understood. We found that windthrows are common in the Amazon region extending from northwest (Peru, Colombia, Venezuela, and west Brazil) to central Brazil, with the highest occurrence of windthrows in the northwest Amazon. More frequent winds, produced by more frequent severe convective systems, in combination with well-known processes that limit the anchoring of trees in the soil, help to explain the higher vulnerability of the northwest Amazon forests to winds. Projected increases in the frequency and intensity of convective storms in the Amazon have the potential to increase wind-related tree mortality. A forest demographic model calibrated for the northwestern and the central Amazon showed that northwestern forests are more resilient to increased wind-related tree mortality than forests in the central Amazon. Our study emphasizes the importance of including wind-related tree mortality in model simulations for reliable predictions of the future of tropical forests and their effects on the Earth' system.
Novel tropical forests Holm, Jennifer A.; Kueppers, Lara M.; Chambers, Jeffrey Q.
New phytologist,
February 2017, Letnik:
213, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Warming climates in the twenty-first century are expected to push tropical ecosystems, which currently reside at the warm and wet edge of bioclimatic life zones, into novel states that have no analog ...on Earth today (Fig. 1). Shifting precipitation patterns will expose some tropical forest regions to more frequent drought conditions that may reduce carbon (C) assimilation and lead to vegetation dieback, and all regions will experience higher temperatures never encountered by extant taxa. At the same time, direct anthropogenic disturbances, such as the hunting of large seed dispersers, use of fire for land management, deforestation, and agricultural land abandonment, are affecting the capacity of forests to mitigate climate change.
Caribbean tropical forests are subject to hurricane disturbances of great variability. In addition to natural storm incongruity, climate change can alter storm formation, duration, frequency, and ...intensity. This model-based investigation assessed the impacts of multiple storms of different intensities and occurrence frequencies on the long-term dynamics of subtropical dry forests in Puerto Rico. Using the previously validated individual-based gap model ZELIG-TROP, we developed a new hurricane damage routine and parameterized it with site- and species-specific hurricane effects. A baseline case with the reconstructed historical hurricane regime represented the control condition. Ten treatment cases, reflecting plausible shifts in hurricane regimes, manipulated both hurricane return time (i.e. frequency) and hurricane intensity. The treatment-related change in carbon storage and fluxes were reported as changes in aboveground forest biomass (AGB), net primary productivity (NPP), and in the aboveground carbon partitioning components, or annual carbon accumulation (ACA). Increasing the frequency of hurricanes decreased aboveground biomass by between 5% and 39%, and increased NPP between 32% and 50%. Decadal-scale biomass fluctuations were damped relative to the control. In contrast, increasing hurricane intensity did not create a large shift in the long-term average forest structure, NPP, or ACA from that of historical hurricane regimes, but produced large fluctuations in biomass. Decreasing both the hurricane intensity and frequency by 50% produced the highest values of biomass and NPP. For the control scenario and with increased hurricane intensity, ACA was negative, which indicated that the aboveground forest components acted as a carbon source. However, with an increase in the frequency of storms or decreased storms, the total ACA was positive due to shifts in leaf production, annual litterfall, and coarse woody debris inputs, indicating a carbon sink into the forest over the long-term. The carbon loss from each hurricane event, in all scenarios, always recovered over sufficient time. Our results suggest that subtropical dry forests will remain resilient to hurricane disturbance. However carbon stocks will decrease if future climates increase hurricane frequency by 50% or more.
PDF
