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Johansson, F.

Publications and source records attributed to Johansson, F..

10 recordsLinked to original sources

A cell type-resolved proteomic atlas of the human body

Proteins define what cells do, yet their systematic quantification across human cell types has remained out of reach. Using Deep Visual Proteomics on tissue from a healthy female donor, we built an atlas of 27 cell types across 14 tissues, quantifying two-thirds of all human protein-coding genes, with up to 8,500 per population. The proteome partitions bimodally into a universal core and highly specialized programs. Integration into the Human Protein Atlas Single Cell Resource enabled comparison of RNA and protein abundance at cell type resolution, revealing that concordance depends on pathway rather than cellular identity. This resolution uncovered cancer-testis antigens in oocytes invisible to bulk profiling. Our openly accessible resource provides a foundation for cell type-resolved proteomics in health and disease.

biochemistry↗

Large-Scale Control of Neuronal Networks In Vitro Using Perforated Microfluidic Devices

Neurons in the brain are organized and connected into complex networks in which electrochemical signaling forms the basis for all brain function. Cortical neuronal net-works are arranged in distinct modular, layered, and hierarchical structures, underlying its diverse functions such as learning, memory, or vision. Modern biotechnology has enabled an array of techniques to culture human neural cells, ranging from discreet co-cultures to complex developmental organoids, but all of which almost exclusively form unstructured and hypersynchronous networks. Overcoming this and capturing the functional and anatomical properties of the brain in vitro has proven to be a great challenge. Current techniques for guiding neuronal connectivity in vitro is often limited to a small fraction of the total population of neural cells, leaving most of the culture effectively unguided. To provide large-scale guidance of neurons in culture, we developed a microtunnel device which allows large-scale cell entry through an array of perforations, and guides neuronal network formation through a series of tunnels. Human neural stem cells capable of forming extensive neuronal projections were used to investigate several different microtunnel designs. One particularity noteworthy design which produced predominantly unidirectional growth was used to successfully validate its effect on propagation of neural activity on microelectrode arrays. Serendipitously, we found that our microtunnels had an extraordinary effect on signal-to-noise ratio and the quality of electrophysiological recordings with regards to number of active channels and detected spikes. Since we often found the neuronal growth surprising, we developed a simple computer model which could reproduce neuronal growth in the various tunnels, allowing computer aided design (CAD) of future projects.

neuroscience↗

The marine microbiome can accurately predict its chemical and biological environment

The microbiome responds to physicochemical changes in the environment, making it a sensitive indicator of ecosystem status. Monitoring microbial communities in aquatic systems is therefore essential for understanding ecosystem health and responses to change. Traditionally reliant on microscopy, monitoring programmes are increasingly incorporating DNA-based approaches leveraging on advances in high-throughput sequencing. In this study, we evaluate the potential of using DNA metabarcoding to predict abiotic and biotic parameters across the spatiotemporal gradients of the Baltic Sea. The dataset comprises 397 seawater samples integrating prokaryotic (16S rRNA gene) and eukaryotic (18S rRNA gene) metabarcoding data with environmental measurements and plankton microscopy counts. Random Forest models based on metabarcoding data accurately predicted a range of physicochemical parameters and showed performance comparably to more complex machine learning algorithms. Models based on 16S rRNA gene data tended to perform better than those based on 18S rRNA gene data, with amplicon sequence variant-level data yielding the best results. Metabarcoding outperformed plankton microscopy in predicting abiotic factors and effectively predicted the presence of phytoplankton and zooplankton genera using [≤]1 L of water. Models trained on independent datasets accurately predicted several of the physicochemical parameters, but performed weaker on others, highlighting the potential and challenges for their transferability. Furthermore, our predictions closely matched the observed HELCOM indicator values for assessing good environmental status, suggesting the utility of microbiome-based approaches in regional marine monitoring frameworks. These findings underscore the potential of environmental DNA as a tool for ecosystem monitoring and management in dynamic coastal systems.

microbiology↗

Intrinsic Diversity in Primary Cilia Revealed Through Spatial Proteomics

Primary cilia are a critical organelle found on most human cells, and their dysfunction is linked to hereditary ciliopathies with a wide phenotypic spectrum. Despite their significance, the specific roles of cilia in different cell types remain poorly understood due to limitations in analyzing ciliary protein composition. We employed antibody-based spatial proteomics to expand the Human Protein Atlas to primary cilia. Our analysis identified the subciliary locations of 715 proteins across three cell lines, examining 128,156 individual cilia. We found that 69% of the ciliary proteome is cell-type specific, and 78% exhibited single-cilia heterogeneity. Our findings portray cilia as sensors tuning their proteome to effectively sense the environment and compute cellular responses. We identified 91 novel cilia proteins and found a genetic candidate variant in CREB3 in one clinical case with features overlapping ciliopathy phenotypes. This open, spatial cilia atlas advances research on cilia and ciliopathies.

cell biology↗

Highly Parallel Tissue Grafting for Combinatorial In Vivo Screening

Material- and cell-based technologies such as engineered tissues hold great promise as human therapies. Yet, the development of many of these technologies becomes stalled at the stage of pre-clinical animal studies due to the tedious and low-throughput nature of in vivo implantation experiments. We introduce a plug and play in vivo screening array platform called Highly Parallel Tissue Grafting (HPTG). HPTG enables parallelized in vivo screening of 43 three-dimensional microtissues within a single 3D printed device. Using HPTG, we screen microtissue formations with varying cellular and material components and identify formulations that support vascular self-assembly, integration and tissue function. Our studies highlight the importance of combinatorial studies that vary cellular and material formulation variables concomitantly, by revealing that inclusion of stromal cells can "rescue" vascular self-assembly in manner that is material-dependent. HPTG provides a route for accelerating pre-clinical progress for diverse medical applications including tissue therapy, cancer biomedicine, and regenerative medicine.

bioengineering↗

Genome-wide single cell annotation of the human protein-coding genes

An important quest for the life science community is to deliver a complete annotation of the human building-blocks of life, the genes and the proteins. Here, we report on a genome-wide effort to annotate all protein-coding genes based on single cell transcriptomics data representing all major tissues and organs in the human body, integrated with data from bulk transcriptomics and antibody-based tissue profiling. Altogether, 25 tissues have been analyzed with single cell transcriptomics resulting in genome-wide expression in 444 single cell types using a strategy involving pooling data from individual cells to obtain genome-wide expression profiles of individual cell type. We introduce a new genome-wide classification tool based on clustering of similar expression profiles across single cell types, which can be visualized using dimensional reduction maps (UMAP). The clustering classification is integrated with a new "tau" score classification for all protein-coding genes, resulting in a measure of single cell specificity across all cell types for all individual genes. The analysis has allowed us to annotate all human protein-coding genes with regards to function and spatial distribution across individual cell types across all major tissues and organs in the human body. A new version of the open access Human Protein Atlas (www.proteinatlas.org) has been launched to enable researchers to explore the new genome-wide annotation on an individual gene level.

systems biology↗

Temporal dynamics of metabolic acquisition in grafted engineered human liver tissue

Liver disease affects millions globally and end-stage liver failure is only cured by organ transplant. Unfortunately, there is a growing shortage of donor organs and disparities in equitable access to transplants among different populations. Less than 10% of global transplantation needs are currently met, highlighting the demand for alternative therapies. Engineered liver tissue grafts that supplement organ function could address these demands. While engineered liver tissues built from human hepatocytes, endothelial cells, and fibroblasts encased in hydrogel have been successfully engrafted in rodent models previously, the extent to which these tissues express human liver metabolic genes and proteins remains unknown. Here, we built engineered human liver tissues and characterized their engraftment, expansion, and metabolic phenotype at sequential stages post-implantation by RNA sequencing, histology, and host serology. Expression of metabolic genes was observed at weeks 1-2, followed by cellular organization into hepatic cords by weeks 4-9.5. Furthermore, grafted engineered tissues exhibited progressive spatially restricted expression of critical functional proteins known to be zonated in the native human liver. To our knowledge, this is the first report of engineered human liver tissue zonation after implantation in vivo, which could have important translational implications for this field.

bioengineering↗

Quantitative properties of the creation and activation of a cell-intrinsic engram

The conditional pause in the spontaneous firing of the cerebellar Purkinje, which determines the timing of the conditional eyeblink response, is mediated by a cell-intrinsic engram (Johansson, et al. 2014) that encodes the interstimulus interval. Our trial-by-trial analysis of the pause parameters reveals that it consists of a single unusually long interspike interval, whose onset and offset latencies are stochastically independent scalar functions of the interstimulus interval. The coefficients of variation are comparable to those observed in the timing of the overt conditional eyeblink. The onsets of the long interspike interval are step changes; there is no prior build-up of inhibition. A single spike volley in the parallel fiber input triggers the read-out of the engram into the long interspike interval; subsequent volleys have no effect on the pause. The high spontaneous firing rate on which the one-interval firing pause supervenes is markedly non-stationary (Fano factors >> 1).

bioinformatics↗

Impact of global warming on insects: are tropical species more vulnerable than temperate species?

The magnitude and ecological impact of climate change varies with latitude. Several recent models have shown that tropical ectotherms face the greatest risk from warming because they currently experience temperatures much closer to their physiological optimum than temperate taxa. Even a small increase in temperature may thus result in steep fitness declines in tropical species but increased fitness in temperate species. This prediction, however, is based on a model that does not account for latitudinal differences in activity periods. Temperate species in particular may often experience considerably higher temperatures than expected during the active season. Here, we integrate data on insect warming tolerance and temperature-dependent development to re-evaluate latitudinal trends in thermal safety margins after accounting for latitudinal trends in insect seasonal activity. Our analyses suggest that temperate and tropical species differ far less in thermal safety margins than commonly assumed, and thus face a similar risk from warming.

ecology↗

Synchronous diversification of Sulawesi’s iconic artiodactyls driven by recent geological events

The high degree of endemism on Sulawesi has previously been suggested to have vicariant origins, dating back 40 Myr ago. Recent studies, however, suggest that much of Sulawesis fauna assembled over the last 15 Myr. Here, we test the hypothesis that recent uplift of previously submerged portions of land on Sulawesi promoted diversification, and that much of the its faunal assemblage is much younger than the island itself. To do so, we combined palaeogeographical reconstructions with genetic and morphometric data sets derived from Sulawesis three largest mammals: the Babirusa, Anoa, and Sulawesi warty pig. Our results indicate that although these species most likely colonized the area that is now Sulawesi at different times (14 Myr ago to 2-3 Myr ago), they experienced an almost synchronous expansion from the central part of the island. Geological reconstructions indicate that this area was above sea level for most of the last 4 Myr, unlike most parts of the island. We conclude that recent emergence of land on Sulawesi (~1-2 Myr) may have allowed species to expand synchronously. Altogether, our results indicates that the establishment of the highly endemic faunal assemblage on Sulawesi was driven by geological events over the last few million years.

evolutionary biology↗