Biology subjects

Nilsson, O.

Publications and source records attributed to Nilsson, O..

8 recordsLinked to original sources

bioRxiv2022

Cytoplasmic HIF-2α correlates to proliferation and predicts worse outcome in sympathetic paraganglioma

Pheochromocytomas (PCCs) and paragangliomas (PGLs) are rare neuroendocrine tumors. PGLs can further be divided into sympathetic (sPGLs) and head-and-neck (HN-PGLs). There are virtually no treatment options, and no cure, for metastatic PCCs and PGLs (PPGLs). Here, we composed a tissue microarray (TMA) consisting of 149 PPGLs, reflecting clinical features and presenting as a useful resource. Mutations in the pseudohypoxic marker EPAS1/HIF-2 correlates to an aggressive tumor phenotype. We show that HIF-2 unexpectedly localized to the cytoplasm in PPGLs. This subcompartmentalized protein expression differed between tumor subtypes, and strongly correlated to proliferation. Half of all sPGLs were metastatic at time of diagnosis. Cytoplasmic HIF-2 was strongly expressed in metastatic sPGLs and predicted poor outcome in this subgroup. We propose that cytoplasmic HIF-2 expression serves as a useful clinical marker to differentiate subtypes and predicting outcome, and hence can be used for improved targeted treatment in PPGLs.

cancer biology↗

bioRxiv2021

Identification of new leaf intrinsic yield genes using cross-species network analysis in plants

With the need to increase plant productivity, one of the challenges plant scientists are facing is to identify genes playing a role in beneficial plant traits. Moreover, even when such genes are found, it is generally not trivial to transfer this knowledge about gene function across species to identify functional orthologs. Here, we focused on the leaf to study plant growth. First, we built leaf growth transcriptional networks in Arabidopsis thaliana, maize (Zea mays), and aspen (Populus tremula). Next, known growth regulators, here defined as genes that when mutated or ectopically expressed alter plant growth, together with cross-species conserved networks, were used as guides to predict novel Arabidopsis growth regulators. Using an in-depth literature screening, 34 out of 100 top predicted growth regulators were confirmed to affect leaf phenotype when mutated or overexpressed and thus represent novel potential growth regulators. Globally, these new growth regulators were involved in cell cycle, plant defense responses, gibberellin, auxin, and brassinosteroid signaling. Phenotypic characterization of loss-of-function lines confirmed two newly predicted growth regulators to be involved in leaf growth (NPF6.4 and LATE MERISTEM IDENTITY2). In conclusion, the presented network approach offers an integrative cross-species strategy to identify new genes involved in plant growth and development. One-sentence summaryCross-species network analysis results in the identification and validation of new growth regulators in Arabidopsis.

plant biology↗

bioRxiv2021

GIGANTEA gene expression influence leaf senescence in Populus in two different ways

GIGANTEA (GI) genes have a central role in plant development and influence several processes such as light signaling, circadian rhythm and abiotic stress tolerance. Hybrid aspen T89 (Populus tremula x tremuloides) trees with low GI expression through RNAi have a severely compromised growth. In order to study the effect of reduced GI expression on leaf traits with special emphasis on leaf senescence, we grafted GI-RNAi scions onto wild type (WT) rootstocks and managed to restore scions growth. The RNAi line had distorted leaf shape and reduced photosynthesis, probably caused by modulating phloem or stomatal function, increased starch accumulation, higher carbon-to-nitrogen (C/N) ratio and a reduced capacity to withstand moderate light stress. GI-RNAi also induced senescence under long day (LD) and moderate light conditions. Furthermore, the GI-RNAi lines were affected in their capacity to respond to "autumn environmental cues" inducing senescence, a type of leaf senescence with characteristics different from senescence induced directly by stress under LD conditions. Whereas Overexpression of GI delayed senescence. The two different effects on leaf senescence were not affected by the expression of FT (Flowering locus T), were "local" - they followed the genotype of the branch independent on the position in the tree - and trees with modified gene expression grown in the field were affected in a similar way as under controlled conditions. Taken together, GI plays a central role to sense the environmental changes during autumn and determine the appropriate timing for leaf senescence in Populus. One sentence summaryLeaf senescence is a complex process that is not well understood, but this paper shows that changing the expression of one gene could influence leaf senescence in Populus trees in two separate ways.

plant biology↗

bioRxiv2020

Rat perichondrium transplanted to articular cartilage defects forms articular-like, hyaline cartilage

Reconstruction of articular surfaces destroyed by infection or trauma is hampered by the lack of suitable graft tissues. Perichondrium autotransplants have been used for this purpose. However, the role of the transplanted perichondrium in the healing of resurfaced joints have not been investigated. Perichondrial and periosteal tissues were harvested from rats hemizygous for a ubiquitously expressed enhanced green fluorescent protein (EGFP) transgene and transplanted into full-thickness articular cartilage defects at the trochlear groove of distal femur in wild-type littermates. As an additional control, cartilage defects were left without a transplant (no transplant control). Distal femurs were collected 3, 14, 56, 112 days after surgery. Transplanted cells and their progenies were readily detected in the defects of perichondrium and periosteum transplanted animals but not in defects left without a transplant. Perichondrium transplants expressed SOX9 and with time differentiated into a hyaline cartilage that expanded and filled out the defects with Col2a1-positive chondrocytes and a matrix rich in proteoglycans. Interestingly, at later timepoints the cartilaginous perichondrium transplants were actively remodeled into bone at the transplant-bone interface and at post-surgery day 112 EGFP-positive perichondrium cells at the articular surface were positive for Prg4. In addition, both perichondrium and periosteum transplants contributed cells to the subchondral bone and bone marrow, suggesting differentiation into osteoblast/osteocytes as well as bone marrow cells. In summary, we found that perichondrium transplanted to articular cartilage defects develops into an articular-like, hyaline cartilage that integrates with the subchondral bone, and is maintained for an extended time. The findings indicate that perichondrium is a suitable tissue for repair and engineering of articular cartilage.

developmental biology↗

bioRxiv2020

Multifocal small intestine neuroendocrine tumors form by independent somatic evolution

BackgroundSmall intestine neuroendocrine tumor (SI-NET), the most common cancer of the small bowel, often displays a curious multifocal phenotype with several intestinal tumors centered around a regional lymph node metastasis. Although SI-NET patients often present with metastatic disease at the time of diagnosis, there is an unusual absence of somatic driver mutations explaining tumor initiation and metastatic spread. The evolutionary trajectories that underlie multifocal SI-NET lesions could provide insight into the underlying tumor biology, but this question remains unresolved. Here, we determined the complete genome sequences of 65 tumor and tissue samples from 11 patients with multifocal SI-NET, allowing for elucidation of phylogenetic relationships between tumors within individual patients. Intra-individual comparisons of whole genome sequences revealed a lack of shared somatic single-nucleotide variants and copy number alterations among the sampled intestinal lesions, supporting that they were of independent clonal origin. Furthermore, each metastasis originated from a single intestinal tumor, and in three of the patients, two independent tumors had metastasized. We conclude that primary multifocal SI-NETs generally arise from clonally independent cells, suggesting a contribution from of a cancer-priming local factor.

genomics↗

bioRxiv2020

Structure dynamics of ApoA-I amyloidogenic variants in small HDL increase their ability to mediate cholesterol efflux

Specific mutations in Apolipoprotein A-I (ApoA-I) of high-density lipoprotein (HDL) are responsible for a late-onset systemic amyloidosis. Carriers do not exhibit increased cardiovascular disease risk despite reduced levels of ApoA-I/ HDL-cholesterol. To explain this paradox, we show that the HDL particle profile of L75P and L174S patients presents a higher relative abundance of the 8.4 nm vs 9.6 nm particles, and that serum from patients, as well as reconstituted 8.4 and 9.6 nm HDL particles (rHDL), possess increased capacity to catalyze cholesterol efflux from macrophages. Synchrotron radiation circular dichroism and hydrogen-deuterium exchange revealed that the variants in 8.4 nm rHDL have altered secondary structure composition and display a more flexible binding to lipids compared to their native counterpart. The reduced HDL-cholesterol levels of patients carrying ApoA-I amyloidogenic variants are thus balanced by higher proportion of small, dense HDL particles and better cholesterol efflux due to altered, region-specific protein structure dynamics.

biochemistry↗

bioRxiv2017

Natural variation at FLOWERING LOCUS T2 mediates local adaptation in a key life history trait in European aspen

BackgroundThe initiation of growth cessation and dormancy represent critical life-history tradeoffs between survival and growth, and have important fitness effects in perennial plants. Such adaptive life history traits often show strong local adaptation along environmental gradients but despite their importance, the genetic architecture of these traits remains poorly understood.\n\nResultsWe integrate whole genome re-sequencing with environmental and phenotypic data from common garden experiments to investigate the genomic basis of local adaptation across a latitudinal gradient in European aspen (Populus tremula). We discover a single genomic region containing the PtFT2 gene that mediates local adaptation in the timing of bud set and that explains 65% of the observed genetic variation in bud set. This locus is the likely target of a recent selective sweep that originated right before or during colonization of northern Scandinavia following the last glaciation. Field and greenhouse experiments confirm that variation in PtFT2 gene expression affect the phenotypic variation in bud set that we observe in wild natural populations.\n\nConclusionsOur results reveal a major effect locus that determine the timing of bud set and that have facilitated rapid adaptation to shorter growing seasons and colder climates in European aspen. The discovery of a single locus explaining a substantial fraction of the variation in a key life history trait is remarkable given that such traits are generally considered to be highly polygenic. These findings provide a dramatic illustration of how loci of large-effect for adaptive traits can arise and be maintained over large geographical scales in natural populations.

evolutionary biology↗

bioRxiv2016

High-spatial-resolution transcriptome profiling reveals uncharacterized regulatory complexity underlying cambial growth and wood formation in Populus tremula

Trees represent the largest terrestrial carbon sink and a renewable source of ligno-cellulose. There is significant scope for yield and quality improvement in these largely undomesticated species, and efforts to engineer new, elite varieties will benefit from an improved understanding of the transcriptional network underlying cambial growth and wood formation. We generated high-spatial-resolution RNA Sequencing data spanning the secondary phloem, vascular cambium and wood forming tissues. The transcriptome comprised 28,294 expressed, previously annotated genes, 78 novel protein-coding genes and 567 long intergenic non-coding RNAs. Most paralogs originating from the Salicaceae whole genome duplication were found to have diverged expression, with the notable exception of those with high expression during secondary cell wall deposition. Co-expression network analysis revealed that the regulation of the transcriptome underlying cambial growth and wood formation comprises numerous modules forming a continuum of active processes across the tissues. The high spatial resolution enabled identification of novel roles for characterised genes involved in xylan and cellulose biosynthesis, regulators of xylem vessel and fiber differentiation and lignification. The associated web resource (AspWood, http://aspwood.popgenie.org) integrates the data within a set of interactive tools for exploring the expression profiles and co-expression network.

plant biology↗