Change search
Link to record
Permanent link

Direct link
BETA
Mollbrink, Annelie
Publications (5 of 5) Show all publications
Newton, P. T., Li, L., Zhou, B., Schweingruber, C., Hovorakova, M., Xie, M., . . . Chagin, A. S. (2019). A radical switch in clonality reveals a stem cell niche in the epiphyseal growth plate. Nature, 567(7747), 234-+
Open this publication in new window or tab >>A radical switch in clonality reveals a stem cell niche in the epiphyseal growth plate
Show others...
2019 (English)In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 567, no 7747, p. 234-+Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP, 2019
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:kth:diva-251299 (URN)10.1038/s41586-019-0989-6 (DOI)000461126600041 ()30814736 (PubMedID)2-s2.0-85062621397 (Scopus ID)
Note

QC 20190509

Available from: 2019-05-09 Created: 2019-05-09 Last updated: 2019-05-09Bibliographically approved
Maniatis, S., Aijo, T., Vickovic, S., Braine, C., Kang, K., Mollbrink, A., . . . Phatnani, H. (2019). Spatiotemporal dynamics of molecular pathology in amyotrophic lateral sclerosis. Science, 364(6435), 89-+
Open this publication in new window or tab >>Spatiotemporal dynamics of molecular pathology in amyotrophic lateral sclerosis
Show others...
2019 (English)In: Science, ISSN 0036-8075, E-ISSN 1095-9203, Vol. 364, no 6435, p. 89-+Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
AMER ASSOC ADVANCEMENT SCIENCE, 2019
National Category
Neurosciences
Identifiers
urn:nbn:se:kth:diva-251500 (URN)10.1126/science.aav9776 (DOI)000463585700040 ()30948552 (PubMedID)2-s2.0-85064324686 (Scopus ID)
Note

QC 20190515

Available from: 2019-05-15 Created: 2019-05-15 Last updated: 2019-05-15Bibliographically approved
Salmén, F., Ståhl, P., Mollbrink, A., Navarro Fernandez, J. C., Vickovic, S., Frisen, J. & Lundeberg, J. (2018). Barcoded solid-phase RNA capture for Spatial Transcriptomics profiling in mammalian tissue sections. Nature Protocols, 13(11), 2501-2534
Open this publication in new window or tab >>Barcoded solid-phase RNA capture for Spatial Transcriptomics profiling in mammalian tissue sections
Show others...
2018 (English)In: Nature Protocols, ISSN 1754-2189, E-ISSN 1750-2799, Vol. 13, no 11, p. 2501-2534Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Nature Publishing Group, 2018
National Category
Biological Sciences
Identifiers
urn:nbn:se:kth:diva-239078 (URN)10.1038/s41596-018-0045-2 (DOI)000448980400004 ()30353172 (PubMedID)2-s2.0-85055531492 (Scopus ID)
Funder
Knut and Alice Wallenberg FoundationSwedish Research CouncilSwedish Foundation for Strategic Research Swedish Cancer SocietyTorsten Söderbergs stiftelseÅke Wiberg FoundationRagnar Söderbergs stiftelse
Note

QC 20181121

Available from: 2018-11-21 Created: 2018-11-21 Last updated: 2019-05-17Bibliographically approved
Lundmark, A., Gerasimcik, N., Båge, T., Jemt, A., Mollbrink, A., Salmén, F., . . . Yucel-Lindberg, T. (2018). Gene expression profiling of periodontitis-affected gingival tissue by spatial transcriptomics. Scientific Reports, 8(1), Article ID 9370.
Open this publication in new window or tab >>Gene expression profiling of periodontitis-affected gingival tissue by spatial transcriptomics
Show others...
2018 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, no 1, article id 9370Article in journal (Refereed) Published
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. 

Place, publisher, year, edition, pages
Nature Publishing Group, 2018
National Category
Biological Sciences
Identifiers
urn:nbn:se:kth:diva-236579 (URN)10.1038/s41598-018-27627-3 (DOI)000435536100046 ()2-s2.0-85048826102 (Scopus ID)
Note

Export Date: 22 October 2018; Article; Correspondence Address: Lundmark, A.; Department of Dental Medicine, Division of Periodontology, Karolinska InstitutetSweden; email: anna.lundmark@ki.se. QC 20181126

Available from: 2018-11-26 Created: 2018-11-26 Last updated: 2018-11-26Bibliographically approved
Davidsson, M., Aldrin-Kirk, P., Cardoso, T., Hartnor, M., Heuer, A., Mollbrink, A., . . . Bjorklund, T. (2018). Mapping the Connectome Using Novel AAV Vectors, DNA Barcoding and Spatial Transcriptomics. Paper presented at 21st Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT), MAY 16-19, 2018, Chicago, IL. Molecular Therapy, 26(5), 319-319
Open this publication in new window or tab >>Mapping the Connectome Using Novel AAV Vectors, DNA Barcoding and Spatial Transcriptomics
Show others...
2018 (English)In: Molecular Therapy, ISSN 1525-0016, E-ISSN 1525-0024, Vol. 26, no 5, p. 319-319Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Cell Press, 2018
National Category
Medical Biotechnology
Identifiers
urn:nbn:se:kth:diva-240242 (URN)000435342204120 ()
Conference
21st Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT), MAY 16-19, 2018, Chicago, IL
Funder
Science for Life Laboratory - a national resource center for high-throughput molecular bioscience
Note

QC 20181214

Available from: 2018-12-14 Created: 2018-12-14 Last updated: 2018-12-14Bibliographically approved
Organisations

Search in DiVA

Show all publications