Biology subjects

Larsson, L.

Publications and source records attributed to Larsson, L..

23 records · Page 2Linked to original sources

bioRxiv2020

Genome-wide Spatial Expression Profiling in FFPE Tissues

Formalin-fixed paraffin embedding (FFPE) is the most widespread long-term tissue preservation approach. Here we present a procedure to perform genome-wide spatial analysis of mRNA in FFPE tissue sections. The procedure takes advantage of well-established, commercially available methods for imaging and spatial barcoding using slides spotted with barcoded oligo(dT) probes to capture the 3 end of mRNA molecules in tissue sections. First, we conducted expression profiling and cell type mapping in coronal sections from the mouse brain to demonstrate the methods capability to delineate anatomical regions from a molecular perspective. Second, we explored the spatial composition of transcriptomic signatures in ovarian carcinosarcoma samples using data driven analysis methods, exemplifying the methods potential to elucidate molecular mechanisms in heterogeneous clinical samples.

genetics↗

bioRxiv2020

Spatial Deconvolution of HER2-positive Breast Tumors Reveals Novel Intercellular Relationships

In the past decades, transcriptomic studies have revolutionized cancer treatment and diagnosis. However, tumor sequencing strategies typically result in loss of spatial information, critical to understand cell interactions and their functional relevance. To address this, we investigate spatial gene expression in HER2-positive breast tumors using Spatial Transcriptomics technology. We show that expression-based clustering enables data-driven tumor annotation and assessment of intra-and interpatient heterogeneity; from which we discover shared gene signatures for immune and tumor processes. We integrate and spatially map tumor-associated types from single cell data to find: segregated epithelial cells, interactions between B and T-cells and myeloid cells, co-localization of macrophage and T-cell subsets. A model is constructed to infer presence of tertiary lymphoid structures, applicable across tissue types and technical platforms. Taken together, we combine different data modalities to define novel interactions between tumor-infiltrating cells in breast cancer and provide tools generalizing across tissues and diseases.

cancer biology↗

bioRxiv2020

Skeletal Muscle Remodeling in Immobilized Patients: Determined Using a Parameter Estimation Histomorphometric Approach

Skeletal muscle biopsy commonly used for light microscopic, electron microscopic and biochemical and transcriptional evaluation remains the gold standard for establishing the etiology of a myopathy. While most myopathies exhibit one or more phenotypes, early stages or several metabolic myopathies often exhibit normal muscle morphology, making diagnosis difficult. In such cases where standard staining techniques fail to offer definitive diagnostic information, a combination of expensive and time-consuming electron microscopy and biochemical testing is required to provide definitive diagnosis. As a step toward overcoming these limitations in diagnostic pathology of skeletal muscle tissue, here we report the application of parameter estimation machine learning approaches on immunofluorescent images of human skeletal muscle tissue acquired using fluorescent microscopy. The machine learning morphometric approach enables the recognition of fine cellular changes in skeletal muscle tissue, allowing determination of skeletal muscle remodeling as a consequence of immobilization.

cell biology↗

bioRxiv2020

Hand-reared wolves show similar, or stronger, attachment toward human caregivers compared to hand-reared dogs

Domesticated animals are generally assumed to display increased sociability towards humans compared to their wild ancestors. Dogs (Canis familiaris) have a remarkable ability to form social relationships with humans, including lasting attachment, a social bond based on emotional dependency. Since it has specifically been suggested that the ability to form attachment with humans evolved post-domestication in dogs, attempts to quantify attachment in wolves (Canis lupus), the ancestor of dogs, have subsequently been performed. However, while these rare wolf studies do highlight the potential for wolves to express attachment behaviour towards humans, the varied, and in some cases, contrasting results also emphasize the need for further testing of wolves. Here we used the standardized Strange Situation Test to investigate attachment behaviour expressed in wolves and dogs hand-reared and socialized under identical conditions. We found that 23 weeks old wolves and dogs equally discriminated between a stranger and a familiar person, and expressed similar attachment behaviours toward a familiar person. Additionally, wolves, but not dogs, expressed significantly elevated stress behaviour during the test, but this stress response was buffered by the presence of a familiar person. Wolves also expressed quantifiable fear responses to the stranger, whereas no such response was detectable in dogs. Together, our results suggest that wolves can show attachment toward humans comparable to that of dogs. Importantly, our findings demonstrate that the ability to form attachment with humans exists in relatives of the wild ancestor of dogs, thus refuting claims that such attachment is unique to post-domestication dog lineages.

animal behavior and cognition↗

bioRxiv2018

Multidimensional transcriptomics provides detailed information about immune cell distribution and identity in HER2+ breast tumors

The comprehensive analysis of tumor tissue heterogeneity is crucial for determining specific disease states and establishing suitable treatment regimes. Here, we analyze tumor tissue sections from ten patients diagnosed with HER2+ breast cancer. We obtain and analyze multidimensional, genome-wide transcriptomics data to resolve spatial immune cell distribution and identity within the tissue sections. Furthermore, we determine the extent of immune cell infiltration in different regions of the tumor tissue, including invasive cancer regions. We combine cross-sectioning and computational alignment to build three-dimensional images of the transcriptional landscape of the tumor and its microenvironment. The three-dimensional data clearly demonstrates the heterogeneous nature of tumor-immune interactions and reveal interpatient differences in immune cell infiltration patterns. Our study shows the potential for an improved stratification and description of the tumor-immune interplay, which is likely to be essential in treatment decisions.

cancer biology↗