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Spatiotemporal dynamics of molecular pathology in amyotrophic lateral sclerosis
New York Genome Ctr, Ctr Genom Neurodegenerat Dis, New York, NY 10013 USA..
Flatiron Inst, Ctr Computat Biol, New York, NY 10010 USA..
KTH, Centres, Science for Life Laboratory, SciLifeLab.ORCID iD: 0000-0003-0985-9885
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..
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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. Vol. 364, no 6435, p. 89-+
National Category
Neurosciences
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URN: urn:nbn:se:kth:diva-251500DOI: 10.1126/science.aav9776ISI: 000463585700040PubMedID: 30948552Scopus ID: 2-s2.0-85064324686OAI: oai:DiVA.org:kth-251500DiVA, id: diva2:1315939
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QC 20190515

Available from: 2019-05-15 Created: 2019-05-15 Last updated: 2019-05-15Bibliographically approved

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Vickovic, SanjaMollbrink, AnnelieAndrusivova, ZanetaSaiz-Castro, GonzaloLundeberg, Joakim

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