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  • 1.
    Davidsson, Marcus
    et al.
    Lund Univ, Mol Neuromodulat, Lund, Sweden..
    Aldrin-Kirk, Patrick
    Lund Univ, Mol Neuromodulat, Lund, Sweden..
    Cardoso, Tiago
    Lund Univ, Dev & Regenerat Neurobiol, Lund, Sweden..
    Hartnor, Morgan
    Lund Univ, Mol Neuromodulat, Lund, Sweden..
    Heuer, Andreas
    Lund Univ, Mol Neuromodulat, Lund, Sweden..
    Mollbrink, Annelie
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Lundeberg, Joakim
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Parmar, Malin
    Lund Univ, Dev & Regenerat Neurobiol, Lund, Sweden..
    Bjorklund, Tomas
    Lund Univ, Mol Neuromodulat, Lund, Sweden..
    Mapping the Connectome Using Novel AAV Vectors, DNA Barcoding and Spatial Transcriptomics2018In: Molecular Therapy, ISSN 1525-0016, E-ISSN 1525-0024, Vol. 26, no 5, p. 319-319Article in journal (Other academic)
  • 2. Lundmark, A.
    et al.
    Gerasimcik, N.
    Båge, T.
    Jemt, A.
    Mollbrink, Annelie
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology. Science for Life Laboratory, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Solna, Sweden.
    Salmén, F.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab. Hubrecht Institute-KNAW (Royal Netherlands Academy of Arts and Sciences) and University Medical Centre Utrecht, Cancer Genomics Netherlands, Utrecht, The Netherlands.
    Lundeberg, Joakim
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology.
    Yucel-Lindberg, T.
    Gene expression profiling of periodontitis-affected gingival tissue by spatial transcriptomics2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, no 1, article id 9370Article in journal (Refereed)
    Abstract [en]

    Periodontitis is a highly prevalent chronic inflammatory disease of the periodontium, leading ultimately to tooth loss. In order to characterize the gene expression of periodontitis-affected gingival tissue, we have here simultaneously quantified and localized gene expression in periodontal tissue using spatial transcriptomics, combining RNA sequencing with histological analysis. Our analyses revealed distinct clusters of gene expression, which were identified to correspond to epithelium, inflamed areas of connective tissue, and non-inflamed areas of connective tissue. Moreover, 92 genes were identified as significantly up-regulated in inflamed areas of the gingival connective tissue compared to non-inflamed tissue. Among these, immunoglobulin lambda-like polypeptide 5 (IGLL5), signal sequence receptor subunit 4 (SSR4), marginal zone B and B1 cell specific protein (MZB1), and X-box binding protein 1 (XBP1) were the four most highly up-regulated genes. These genes were also verified as significantly higher expressed in gingival tissue of patients with periodontitis compared to healthy controls, using reverse transcription quantitative polymerase chain reaction. Moreover, the protein expressions of up-regulated genes were verified in gingival biopsies by immunohistochemistry. In summary, in this study, we report distinct gene expression signatures within periodontitis-affected gingival tissue, as well as specific genes that are up-regulated in inflamed areas compared to non-inflamed areas of gingival tissue. The results obtained from this study may add novel information on the genes and cell types contributing to pathogenesis of the chronic inflammatory disease periodontitis. 

  • 3.
    Maniatis, Silas
    et al.
    New York Genome Ctr, Ctr Genom Neurodegenerat Dis, New York, NY 10013 USA..
    Aijo, Tarmo
    Flatiron Inst, Ctr Computat Biol, New York, NY 10010 USA..
    Vickovic, Sanja
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Braine, Catherine
    New York Genome Ctr, Ctr Genom Neurodegenerat Dis, New York, NY 10013 USA.;Columbia Univ, Mortimer B Zuckerman Mind Brain Behav Inst, New York, NY 10032 USA..
    Kang, Kristy
    New York Genome Ctr, Ctr Genom Neurodegenerat Dis, New York, NY 10013 USA..
    Mollbrink, Annelie
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Fagegaltier, Delphine
    New York Genome Ctr, Ctr Genom Neurodegenerat Dis, New York, NY 10013 USA..
    Andrusivova, Zaneta
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Saarenpaa, Sami
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Saiz-Castro, Gonzalo
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Cuevas, Miguel
    Columbia Univ, Mortimer B Zuckerman Mind Brain Behav Inst, New York, NY 10032 USA..
    Watters, Aaron
    Flatiron Inst, Ctr Computat Biol, New York, NY 10010 USA..
    Lundeberg, Joakim
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology.
    Bonneau, Richard
    Flatiron Inst, Ctr Computat Biol, New York, NY 10010 USA.;NYU, Ctr Data Sci, New York, NY 10011 USA..
    Phatnani, Hemali
    New York Genome Ctr, Ctr Genom Neurodegenerat Dis, New York, NY 10013 USA.;Columbia Univ, Mortimer B Zuckerman Mind Brain Behav Inst, New York, NY 10032 USA..
    Spatiotemporal dynamics of molecular pathology in amyotrophic lateral sclerosis2019In: Science, ISSN 0036-8075, E-ISSN 1095-9203, Vol. 364, no 6435, p. 89-+Article in journal (Refereed)
    Abstract [en]

    Paralysis occurring in amyotrophic lateral sclerosis (ALS) results from denervation of skeletal muscle as a consequence of motor neuron degeneration. Interactions between motor neurons and glia contribute to motor neuron loss, but the spatiotemporal ordering of molecular events that drive these processes in intact spinal tissue remains poorly understood. Here, we use spatial transcriptomics to obtain gene expression measurements of mouse spinal cords over the course of disease, as well as of postmortem tissue from ALS patients, to characterize the underlying molecular mechanisms in ALS. We identify pathway dynamics, distinguish regional differences between microglia and astrocyte populations at early time points, and discern perturbations in several transcriptional pathways shared between murine models of ALS and human postmortem spinal cords.

  • 4.
    Newton, Phillip T.
    et al.
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.;Karolinska Univ Hosp, Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.;Karolinska Univ Hosp, Pediat Endocrinol Unit, Stockholm, Sweden..
    Li, Lei
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
    Zhou, Baoyi
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
    Schweingruber, Christoph
    Karolinska Inst, Dept Neurosci, Stockholm, Sweden..
    Hovorakova, Maria
    Czech Acad Sci, Inst Expt Med, Dept Dev Biol, Prague, Czech Republic..
    Xie, Meng
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
    Sun, Xiaoyan
    Karolinska Inst, Dept Biosci & Nutr, Huddinge, Sweden.;Karolinska Inst, Ctr Innovat Med, Huddinge, Sweden..
    Sandhow, Lakshmi
    Karolinska Inst, Ctr Hematol & Regenerat Med, Huddinge, Sweden..
    Artemov, Artem V.
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.;Sechenov First Moscow State Med Univ, Inst Regenerat Med, Moscow, Russia..
    Ivashkin, Evgeny
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
    Suter, Simon
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
    Dyachuk, Vyacheslav
    Karolinska Inst, Dept Neurosci, Stockholm, Sweden.;Russian Acad Sci, Far Eastern Branch, Natl Sci Ctr Marine Biol, Vladivostok, Russia..
    El Shahawy, Maha
    Univ Gothenburg, Sahlgrenska Acad, Dept Oral Biochem, Gothenburg, Sweden..
    Gritli-Linde, Amel
    Univ Gothenburg, Sahlgrenska Acad, Dept Oral Biochem, Gothenburg, Sweden..
    Bouderlique, Thibault
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
    Petersen, Julian
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.;Med Univ Vienna, Ctr Brain Res, Dept Mol Neurosci, Vienna, Austria..
    Mollbrink, Annelie
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Lundeberg, Joakim
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology.
    Enikolopov, Grigori
    SUNY Stony Brook, Ctr Dev Genet, Stony Brook, NY 11794 USA.;SUNY Stony Brook, Dept Anesthesiol, Stony Brook, NY 11794 USA..
    Qian, Hong
    Karolinska Inst, Ctr Hematol & Regenerat Med, Huddinge, Sweden..
    Fried, Kaj
    Karolinska Inst, Dept Neurosci, Stockholm, Sweden..
    Kasper, Maria
    Karolinska Inst, Dept Biosci & Nutr, Huddinge, Sweden.;Karolinska Inst, Ctr Innovat Med, Huddinge, Sweden..
    Hedlund, Eva
    Karolinska Inst, Dept Neurosci, Stockholm, Sweden..
    Adameyko, Igor
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.;Med Univ Vienna, Ctr Brain Res, Dept Mol Neurosci, Vienna, Austria..
    Savendahl, Lars
    Karolinska Univ Hosp, Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.;Karolinska Univ Hosp, Pediat Endocrinol Unit, Stockholm, Sweden..
    Chagin, Andrei S.
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.;Sechenov First Moscow State Med Univ, Inst Regenerat Med, Moscow, Russia..
    A radical switch in clonality reveals a stem cell niche in the epiphyseal growth plate2019In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 567, no 7747, p. 234-+Article in journal (Refereed)
    Abstract [en]

    Longitudinal bone growth in children is sustained by growth plates, narrow discs of cartilage that provide a continuous supply of chondrocytes for endochondral ossification 1 . However, it remains unknown how this supply is maintained throughout childhood growth. Chondroprogenitors in the resting zone are thought to be gradually consumed as they supply cells for longitudinal growth 1,2 , but this model has never been proved. Here, using clonal genetic tracing with multicolour reporters and functional perturbations, we demonstrate that longitudinal growth during the fetal and neonatal periods involves depletion of chondroprogenitors, whereas later in life, coinciding with the formation of the secondary ossification centre, chondroprogenitors acquire the capacity for self-renewal, resulting in the formation of large, stable monoclonal columns of chondrocytes. Simultaneously, chondroprogenitors begin to express stem cell markers and undergo symmetric celldivision. Regulation of the pool of self-renewing progenitors involves the hedgehog and mammalian target of rapamycin complex 1 (mTORC1) signalling pathways. Our findings indicate that a stem cell niche develops postnatally in the epiphyseal growth plate, which provides a continuous supply of chondrocytes over a prolonged period.

  • 5.
    Salmén, Fredrik
    et al.
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology.
    Ståhl, Patrik
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Mollbrink, Annelie
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Navarro Fernandez, José Carlos
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Vickovic, Sanja
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Frisen, Jonas
    Karolinska Inst, Dept Cell & Mol Biol, Stockholm, Sweden..
    Lundeberg, Joakim
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology.
    Barcoded solid-phase RNA capture for Spatial Transcriptomics profiling in mammalian tissue sections2018In: Nature Protocols, ISSN 1754-2189, E-ISSN 1750-2799, Vol. 13, no 11, p. 2501-2534Article in journal (Refereed)
    Abstract [en]

    Spatial resolution of gene expression enables gene expression events to be pinpointed to a specific location in biological tissue. Spatially resolved gene expression in tissue sections is traditionally analyzed using immunohistochemistry (IHC) or in situ hybridization (ISH). These technologies are invaluable tools for pathologists and molecular biologists; however, their throughput is limited to the analysis of only a few genes at a time. Recent advances in RNA sequencing (RNA-seq) have made it possible to obtain unbiased high-throughput gene expression data in bulk. Spatial Transcriptomics combines the benefits of traditional spatially resolved technologies with the massive throughput of RNA-seq. Here, we present a protocol describing how to apply the Spatial Transcriptomics technology to mammalian tissue. This protocol combines histological staining and spatially resolved RNA-seq data from intact tissue sections. Once suitable tissue-specific conditions have been established, library construction and sequencing can be completed in similar to 5-6 d. Data processing takes a few hours, with the exact timing dependent on the sequencing depth. Our method requires no special instruments and can be performed in any laboratory with access to a cryostat, microscope and next-generation sequencing.

1 - 5 of 5
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