| 1. |
- Camacho, Carlos, et al.
(författare)
-
Leucistic plumage as a result of progressive greying in a cryptic nocturnal bird
- 2022
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 12:1
-
Tidskriftsartikel (refereegranskat)abstract
- Leucism, broadly defined as the lack of melanin pigmentation, occurs in many animal species. Most studies on leucism and other colour aberrations are based on opportunistic observations or small cross-sectional samples, thus limiting our ability to produce reliable results and test theoretical predictions. This study combines cross-sectional and longitudinal data collected in 2016–2020 from a population of red-necked nightjars (Caprimulgus ruficollis). The goals of the study are (i) to investigate sex and age effects on partial leucism, (ii) to separate within-subject effects (progressive greying) from between-subject effects (selective disappearance), and (iii) to examine differences in body mass, structural size, and life span between leucistic and non-leucistic individuals. The probability of leucism in nightjars increased from juveniles to adults at similar rates in males and females. Our longitudinal analysis and life-span comparisons indicated a minor contribution of selective disappearance to age-related changes in leucism, but rather suggested that the loss of melanin from feathers can be attributed to progressive greying in ageing adults. Body mass and size were consistently smaller (5% and 1.5%, respectively) in leucistic than in non-leucistic nightjars, although the reason for this difference remains unclear. Our study sheds light on the sources and mechanisms of variation in leucism in natural populations and its relationship with important life-history traits, such as life span.
|
|
| 2. |
- Emdal, Kristina B., et al.
(författare)
-
Phosphoproteomics of primary AML patient samples reveals rationale for AKT combination therapy and p53 context to overcome selinexor resistance
- 2022
-
Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 40:6
-
Tidskriftsartikel (refereegranskat)abstract
- Acute myeloid leukemia (AML) is a heterogeneous disease with variable patient responses to therapy. Selinexor, an inhibitor of nuclear export, has shown promising clinical activity for AML. To identify the molecular context for monotherapy sensitivity as well as rational drug combinations, we profile selinexor signaling responses using phosphoproteomics in primary AML patient samples and cell lines. Functional phosphosite scoring reveals that p53 function is required for selinexor sensitivity consistent with enhanced efficacy of selinexor in combination with the MDM2 inhibitor nutlin-3a. Moreover, combining selinexor with the AKT inhibitor MK-2206 overcomes dysregulated AKT-FOXO3 signaling in resistant cells, resulting in synergistic anti-proliferative effects. Using high-throughput spatial proteomics to profile subcellular compartments, we measure global proteome and phospho-proteome dynamics, providing direct evidence of nuclear translocation of FOXO3 upon combination treatment. Our data demonstrate the potential of phosphoproteomics and functional phosphorylation site scoring to successfully pinpoint key targetable signaling hubs for rational drug combinations.
|
|
| 3. |
- Engblom, Camilla, et al.
(författare)
-
Spatial transcriptomics of B cell and T cell receptors reveals lymphocyte clonal dynamics
- 2023
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 382:6675, s. 8486-
-
Tidskriftsartikel (refereegranskat)abstract
- The spatial distribution of lymphocyte clones within tissues is critical to their development, selection, and expansion. We have developed spatial transcriptomics of variable, diversity, and joining (VDJ) sequences (Spatial VDJ), a method that maps B cell and T cell receptor sequences in human tissue sections. Spatial VDJ captures lymphocyte clones that match canonical B and T cell distributions and amplifies clonal sequences confirmed by orthogonal methods. We found spatial congruency between paired receptor chains, developed a computational framework to predict receptor pairs, and linked the expansion of distinct B cell clones to different tumor-associated gene expression programs. Spatial VDJ delineates B cell clonal diversity and lineage trajectories within their anatomical niche. Thus, Spatial VDJ captures lymphocyte spatial clonal architecture across tissues, providing a platform to harness clonal sequences for therapy.
|
|
| 4. |
- Frede, Annika, et al.
(författare)
-
B cell expansion hinders the stroma-epithelium regenerative cross talk during mucosal healing
- 2022
-
Ingår i: Immunity. - : Elsevier BV. - 1074-7613 .- 1097-4180. ; 55:12, s. 2336-
-
Tidskriftsartikel (refereegranskat)abstract
- Therapeutic promotion of intestinal regeneration holds great promise, but defining the cellular mechanisms that influence tissue regeneration remains an unmet challenge. To gain insight into the process of mucosal healing, we longitudinally examined the immune cell composition during intestinal damage and regeneration. B cells were the dominant cell type in the healing colon, and single-cell RNA sequencing (scRNA-seq) re-vealed expansion of an IFN-induced B cell subset during experimental mucosal healing that predominantly located in damaged areas and associated with colitis severity. B cell depletion accelerated recovery upon injury, decreased epithelial ulceration, and enhanced gene expression programs associated with tissue re-modeling. scRNA-seq from the epithelial and stromal compartments combined with spatial transcriptomics and multiplex immunostaining showed that B cells decreased interactions between stromal and epithelial cells during mucosal healing. Activated B cells disrupted the epithelial-stromal cross talk required for orga-noid survival. Thus, B cell expansion during injury impairs epithelial-stromal cell interactions required for mucosal healing, with implications for the treatment of IBD.
|
|
| 5. |
- Hidalgo-Rodríguez, Paula, et al.
(författare)
-
Body mass dynamics of migratory nightjars are explained by individual turnover and fueling
- 2021
-
Ingår i: Behavioral Ecology. - : Oxford University Press (OUP). - 1045-2249 .- 1465-7279. ; 32:6, s. 1086-1093
-
Tidskriftsartikel (refereegranskat)abstract
- Body mass is a commonly used indicator of the energy stores of migratory animals and there is considerable evidence that it is a critical determinant of migration decisions and outcomes. Mean population mass often increases during the post-breeding period in most migratory species. Usually, this increase is interpreted as the result of fuel accumulation for migration based on the assumption that mean population mass mirrors mean individual mass. However, an empirical test of this assumption is lacking, and it is unknown whether the general increase in mean population mass is entirely the result of within-individual mass gain, or if it rather reflects a change in the nature of individuals in the population (mass-dependent turnover). We investigated changes in body mass during the post-fledging period of a migratory bird, the Red-necked Nightjar (Caprimulgus ruficollis), and combined longitudinal and cross-sectional data collected over 9 years to disentangle the relative contribution of individual-level (mass gain) and population-level (selective appearance and disappearance) processes. We found that the average body mass of fully-developed juveniles increased as the season progressed and that both individual mass gain and the selective disappearance of lighter individuals contributed to this increase. Contrary to the general expectations for migrants, the turnover of individuals contributed 3.5 times more to the seasonal increase in average body mass than individual mass gain. On a practical note, this differential contribution implied a discrepancy of over 40% between the time-average rates of mass gain (fuel deposition rates) estimated from population-level and individual-level data. Our study calls for caution in the use of population-level changes in body mass to make inferences about individual fuel deposition rates and, more generally, indicates that longitudinal and cross-sectional approaches need to be combined to uncover phenotype-time correlations in natural populations.
|
|
| 6. |
- Karlsson, Max
(författare)
-
Mapping and annotating the mammalian body-wide protein-coding gene expression
- 2022
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- A central aim of fundamental research is to create conditions necessary for fueling further research and innovation. Our understanding of basic biology is central for future developments of tools for diagnosing, monitoring, and treating disease. This doctoral thesis focuses on mapping the mammalian protein-coding gene expression in healthy cells and tissues, and annotation of genes based on their expression patterns, specificity, location, and function. This has in large part been achieved by using large scale transcriptomic and proteomic profiling to describe the gene expression landscape that defines the identities of the great diversity of cells present in mammals. Characterization of gene expression across different tissues and cell types provide fundamental tools to enable the exploration, summary, and ultimately, the annotation of the mammalian proteome, which is still incomplete.The studies comprising this thesis have contributed to the Human Protein Atlas, an online open-access portal for proteomic and transcriptomic data, with the aim to profile each human protein-coding gene to create a spatial map of the molecular organization of the human body, providing basic tools for the scientific community. Paper I comprises an effort to catalogue all proteins that are actively secreted from cells; defining the human secretome. Paper II entails the deep characterization and annotation of the protein-coding transcriptome of 18 peripheral immune cell types. Paper III describes the, to date, most comprehensive tissue-based transcriptomic profiling of protein-coding genes in 98 tissues of the increasingly important model animal pig. Paper IV extends previous tissue-based maps of the human protein-coding genome by integration of 13 single cell transcriptome datasets. Paper V explores the human protein-coding genome in a clustering-based annotation of co-expressed genes across single cells and tissues to provide a framework for finding previously unknown functional relationships between genes by the principle of “guilt-by-association”.In summary, the work described here entails a small contribution to the grand effort of spatially mapping proteins across tissues and cell types, for building a framework of biological knowledge that can lead to increased understanding of the constituents that make us humans.
|
|
| 7. |
- Masarapu, Yuvarani, et al.
(författare)
-
Spatially resolved multiomics on the neuronal effects induced by spaceflight in mice
- 2024
-
Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1
-
Tidskriftsartikel (refereegranskat)abstract
- Impairment of the central nervous system (CNS) poses a significant health risk for astronauts during long-duration space missions. In this study, we employed an innovative approach by integrating single-cell multiomics (transcriptomics and chromatin accessibility) with spatial transcriptomics to elucidate the impact of spaceflight on the mouse brain in female mice. Our comparative analysis between ground control and spaceflight-exposed animals revealed significant alterations in essential brain processes including neurogenesis, synaptogenesis and synaptic transmission, particularly affecting the cortex, hippocampus, striatum and neuroendocrine structures. Additionally, we observed astrocyte activation and signs of immune dysfunction. At the pathway level, some spaceflight-induced changes in the brain exhibit similarities with neurodegenerative disorders, marked by oxidative stress and protein misfolding. Our integrated spatial multiomics approach serves as a stepping stone towards understanding spaceflight-induced CNS impairments at the level of individual brain regions and cell types, and provides a basis for comparison in future spaceflight studies. For broader scientific impact, all datasets from this study are available through an interactive data portal, as well as the National Aeronautics and Space Administration (NASA) Open Science Data Repository (OSDR).
|
|
| 8. |
- Ostaszewski, Marek, et al.
(författare)
-
COVID19 Disease Map, a computational knowledge repository of virus-host interaction mechanisms
- 2021
-
Ingår i: Molecular Systems Biology. - : John Wiley & Sons. - 1744-4292 .- 1744-4292. ; 17:10
-
Tidskriftsartikel (refereegranskat)abstract
- We need to effectively combine the knowledge from surging literature with complex datasets to propose mechanistic models of SARS-CoV-2 infection, improving data interpretation and predicting key targets of intervention. Here, we describe a large-scale community effort to build an open access, interoperable and computable repository of COVID-19 molecular mechanisms. The COVID-19 Disease Map (C19DMap) is a graphical, interactive representation of disease-relevant molecular mechanisms linking many knowledge sources. Notably, it is a computational resource for graph-based analyses and disease modelling. To this end, we established a framework of tools, platforms and guidelines necessary for a multifaceted community of biocurators, domain experts, bioinformaticians and computational biologists. The diagrams of the C19DMap, curated from the literature, are integrated with relevant interaction and text mining databases. We demonstrate the application of network analysis and modelling approaches by concrete examples to highlight new testable hypotheses. This framework helps to find signatures of SARS-CoV-2 predisposition, treatment response or prioritisation of drug candidates. Such an approach may help deal with new waves of COVID-19 or similar pandemics in the long-term perspective.
|
|
| 9. |
- Parigi, Sara M., et al.
(författare)
-
The spatial transcriptomic landscape of the healing mouse intestine following damage
- 2022
-
Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 13:1
-
Tidskriftsartikel (refereegranskat)abstract
- The colon is comprised of specialized cells that interact with each other to function, however, the molecular regionalization of the colon is incompletely understood. Here, the authors use spatial transcriptomics to generate a publicly available resource defining the transcriptomic regionalization of the colon during steady state and mucosal healing. The intestinal barrier is composed of a complex cell network defining highly compartmentalized and specialized structures. Here, we use spatial transcriptomics to define how the transcriptomic landscape is spatially organized in the steady state and healing murine colon. At steady state conditions, we demonstrate a previously unappreciated molecular regionalization of the colon, which dramatically changes during mucosal healing. Here, we identified spatially-organized transcriptional programs defining compartmentalized mucosal healing, and regions with dominant wired pathways. Furthermore, we showed that decreased p53 activation defined areas with increased presence of proliferating epithelial stem cells. Finally, we mapped transcriptomics modules associated with human diseases demonstrating the translational potential of our dataset. Overall, we provide a publicly available resource defining principles of transcriptomic regionalization of the colon during mucosal healing and a framework to develop and progress further hypotheses.
|
|
