28 research outputs found
Single-cell transcriptomics to explore the immune system in health and disease
The immune system varies in cell types, states, and locations. The complex networks, interactions, and responses of immune cells produce diverse cellular ecosystems composed of multiple cell types, accompanied by genetic diversity in antigen receptors. Within this ecosystem, innate and adaptive immune cells maintain and protect tissue function, integrity, and homeostasis upon changes in functional demands and diverse insults. Characterizing this inherent complexity requires studies at single-cell resolution. Recent advances such as massively parallel single-cell RNA sequencing and sophisticated computational methods are catalyzing a revolution in our understanding of immunology. Here we provide an overview of the state of single-cell genomics methods and an outlook on the use of single-cell techniques to decipher the adaptive and innate components of immunity.National Institute of Allergy and Infectious Diseases (U.S.) (Grant U24AI118672)National Institute of Allergy and Infectious Diseases (U.S.) (Grant R24AI072073
Local and regional drivers influence how aquatic community diversity, resistance and resilience vary in response to drying
Disturbance events govern how the biodiversity of ecological communities varies in both space and time. In freshwater ecosystems, there is evidence that local and regionalâscale drivers interact to influence ecological responses to drying disturbances. However, most research provides temporal snapshots at the local scale, whereas few studies encompass a gradient of drying severity spanning multiple years. Using a dataset of rare spatiotemporal extent and detail, we demonstrate how independent and interacting local and regionalâscale factors drive shifts in the α and ÎČ diversities of communities in dynamic river ecosystems. We examined aquatic invertebrate assemblage responses to hydrological variability (as characterized by monthly observations of instream conditions) at 30 sites over a 12âyear period encompassing typical years and two severe drought disturbances. Sites varied in their disturbance regimes and hydrological connectivity at both local (i.e. siteâspecific) and regional (i.e. river catchment) scales. Whereas α diversity was mainly influenced by local factors including flow permanence and the temporal extent of ponded and dry conditions, both temporal and spatial ÎČ diversities also responded to regionalâscale metrics such as the spatial extent of flow and hydrological connectivity. We observed stronger local negative responses for taxa with lower capacities to tolerate drying (i.e. resistance) and/or to recover after flow resumes (i.e. resilience), whereas taxa with functional traits promoting resilience made an increasing contribution to spatial ÎČ diversity as hydrological connectivity declined. As droughts increase in extent and severity across global regions, our findings highlight the functional basis of taxonomic responses to disturbance and connectivity, and thus advance understanding of how drying disturbances shape biodiversity in river networks. Our identification of the role of regional hydrological factors could inform catchmentâscale management strategies that support ecosystem resilience in a context of global change
T cell fate and clonality inference from single-cell transcriptomes.
We developed TraCeR, a computational method to reconstruct full-length, paired T cell receptor (TCR) sequences from T lymphocyte single-cell RNA sequence data. TraCeR links T cell specificity with functional response by revealing clonal relationships between cells alongside their transcriptional profiles. We found that T cell clonotypes in a mouse Salmonella infection model span early activated CD4(+) T cells as well as mature effector and memory cells
Single-cell RNA-seq and computational analysis using temporal mixture modeling resolves TH1/TFH fate bifurcation in malaria
Simulating rewetting events in intermittent rivers and ephemeral streams: A global analysis of leached nutrients and organic matter
Climate change and human pressures are changing the global distribution and the exâ
tent of intermittent rivers and ephemeral streams (IRES), which comprise half of the
global river network area. IRES are characterized by periods of flow cessation, during
which channel substrates accumulate and undergo physicoâchemical changes (preconâ
ditioning), and periods of flow resumption, when these substrates are rewetted and
release pulses of dissolved nutrients and organic matter (OM). However, there are no
estimates of the amounts and quality of leached substances, nor is there information
on the underlying environmental constraints operating at the global scale. We experiâ
mentally simulated, under standard laboratory conditions, rewetting of leaves, riverâ
bed sediments, and epilithic biofilms collected during the dry phase across 205 IRES
from five major climate zones. We determined the amounts and qualitative characterâ
istics of the leached nutrients and OM, and estimated their areal fluxes from riverbeds.
In addition, we evaluated the variance in leachate characteristics in relation to selected
environmental variables and substrate characteristics. We found that sediments, due
to their large quantities within riverbeds, contribute most to the overall flux of disâ
solved substances during rewetting events (56%â98%), and that flux rates distinctly
differ among climate zones. Dissolved organic carbon, phenolics, and nitrate contribâ
uted most to the areal fluxes. The largest amounts of leached substances were found
in the continental climate zone, coinciding with the lowest potential bioavailability of
the leached OM. The opposite pattern was found in the arid zone. Environmental variâ
ables expected to be modified under climate change (i.e. potential evapotranspiration,
aridity, dry period duration, land use) were correlated with the amount of leached subâ
stances, with the strongest relationship found for sediments. These results show that
the role of IRES should be accounted for in global biogeochemical cycles, especially
because prevalence of IRES will increase due to increasing severity of drying event
Simulating rewetting events in intermittent rivers and ephemeral streams: a global analysis of leached nutrients and organic matter
Climate change and human pressures are changing the global distribution and extent of intermittent rivers and ephemeral streams (IRES), which comprise half of the global river network area. IRES are characterized by periods of flow cessation, during which channel substrates accumulate and undergo physicoâchemical changes (preconditioning), and periods of flow resumption, when these substrates are rewetted and release pulses of dissolved nutrients and organic matter (OM). However, there are no estimates of the amounts and quality of leached substances, nor is there information on the underlying environmental constraints operating at the global scale. We experimentally simulated, under standard laboratory conditions, rewetting of leaves, riverbed sediments, and epilithic biofilms collected during the dry phase across 205 IRES from five major climate zones. We determined the amounts and qualitative characteristics of the leached nutrients and OM, and estimated their areal fluxes from riverbeds. In addition, we evaluated the variance in leachate characteristics in relation to selected environmental variables and substrate characteristics. We found that sediments, due to their large quantities within riverbeds, contribute most to the overall flux of dissolved substances during rewetting events (56â98%), and that flux rates distinctly differ among climate zones. Dissolved organic carbon, phenolics, and nitrate contributed most to the areal fluxes. The largest amounts of leached substances were found in the continental climate zone, coinciding with the lowest potential bioavailability of the leached organic matter. The opposite pattern was found in the arid zone. Environmental variables expected to be modified under climate change (i.e. potential evapotranspiration, aridity, dry period duration, land use) were correlated with the amount of leached substances, with the strongest relationship found for sediments. These results show that the role of IRES should be accounted for in global biogeochemical cycles, especially because prevalence of IRES will increase due to increasing severity of drying events
Are cells from a snowman realistic? Cryopreserved tissues as a source for single-cell RNA-sequencing experiments
A recently published study in Genome Biology shows that cells isolated from cryopreserved tissues are a reliable source of genetic material for single-cell RNA-sequencing experiments.Please see related Method article: http://genomebiology.biomedcentral.com/articles/10.1186/s13059-017-1171-9
Single-cell analysis at the threshold
A discussion of some of the challenges and promise of single-cell technology