MedicGo
Spatial Transcriptomics and In Situ Sequencing to Study Alzheimer's Disease.
Metadata
Journalcell38.637Date
2020 Jul 17
a month ago
Publication Type
Journal Article
Volume
2020-Jul-17 / :
Author
Chen WT 1, Lu A 1, Craessaerts K 1, Pavie B 2, Sala Frigerio C 3, Corthout N 2, Qian X 4, Laláková J 4, Kühnemund M 4, Voytyuk I 1, Wolfs L 1, Mancuso R 1, Salta E 1, Balusu S 1, Snellinx A 1, Munck S 2, Jurek A 5, Fernandez Navarro J 5, Saido TC 6, Huitinga I 7, Lundeberg J 5, Fiers M 8, De Strooper B 9
Affiliation
  • 2. VIB Center for Brain & Disease Research, Leuven 3000, Belgium; KU Leuven, Department of Neurosciences, Leuven Brain Institute, Leuven 3000, Belgium; VIB Bio Imaging Core, Gent 9052, Belgium; VIB Bio Imaging Core, Leuven 3000, Belgium.
  • 3. VIB Center for Brain & Disease Research, Leuven 3000, Belgium; KU Leuven, Department of Neurosciences, Leuven Brain Institute, Leuven 3000, Belgium; UK Dementia Research Institute at University College London, London WC1E 6BT, UK.
  • 4. Cartana AB, Nobels väg 16, Solna 17165, Sweden.
  • 5. Science for Life Laboratory, Department of Gene Technology, KTH Royal Institute of Technology, Solna, Stockholm 17121, Sweden.
  • 6. Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, Wako-shi, Saitama 351-0198, Japan.
  • 7. Department of Neuroimmunology, Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, Amsterdam 1105BA, the Netherlands; Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam 1098XH, the Netherlands.
  • 8. VIB Center for Brain & Disease Research, Leuven 3000, Belgium; KU Leuven, Department of Neurosciences, Leuven Brain Institute, Leuven 3000, Belgium; UK Dementia Research Institute at University College London, London WC1E 6BT, UK. Electronic address: [email protected]
  • 9. VIB Center for Brain & Disease Research, Leuven 3000, Belgium; KU Leuven, Department of Neurosciences, Leuven Brain Institute, Leuven 3000, Belgium; UK Dementia Research Institute at University College London, London WC1E 6BT, UK. Electronic address: [email protected]
Doi
PMIDMESH
Abstract
Although complex inflammatory-like alterations are observed around the amyloid plaques of Alzheimer's disease (AD), little is known about the molecular changes and cellular interactions that characterize this response. We investigate here, in an AD mouse model, the transcriptional changes occurring in tissue domains in a 100-μm diameter around amyloid plaques using spatial transcriptomics. We demonstrate early alterations in a gene co-expression network enriched for myelin and oligodendrocyte genes (OLIGs), whereas a multicellular gene co-expression network of plaque-induced genes (PIGs) involving the complement system, oxidative stress, lysosomes, and inflammation is prominent in the later phase of the disease. We confirm the majority of the observed alterations at the cellular level using in situ sequencing on mouse and human brain sections. Genome-wide spatial transcriptomics analysis provides an unprecedented approach to untangle the dysregulated cellular network in the vicinity of pathogenic hallmarks of AD and other brain diseases.
Keywords: Alzheimer’s disease amyloid plaque astrocyte cellular phase complement cascade in situ sequencing microglia myelination oligodendrocyte spatial transcriptomics
Fav
Like
Download
Share
Export
Cite
38.6
Cellcell
Metadata
LocationUnited States
FromCELL PRESS

No Data

© 2017 - 2020 Medicgo
Powered by some medical students