Spatiotemporal dynamics of molecular pathology in amyotrophic lateral sclerosis

Silas Maniatis, Tarmo Äijö, Sanja Vickovic, Catherine Braine, Kristy Kang, Annelie Mollbrink, Delphine Fagegaltier, Žaneta Andrusivová, Sami Saarenpää, Gonzalo Saiz-Castro, Miguel Cuevas, Aaron Watters, Joakim Lundeberg, Richard Bonneau, Hemali Phatnani

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)89-93
Number of pages5
JournalScience
Volume364
Issue number6435
DOIs
StatePublished - Apr 5 2019

ASJC Scopus subject areas

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    Maniatis, S., Äijö, T., Vickovic, S., Braine, C., Kang, K., Mollbrink, A., Fagegaltier, D., Andrusivová, Ž., Saarenpää, S., Saiz-Castro, G., Cuevas, M., Watters, A., Lundeberg, J., Bonneau, R., & Phatnani, H. (2019). Spatiotemporal dynamics of molecular pathology in amyotrophic lateral sclerosis. Science, 364(6435), 89-93. https://doi.org/10.1126/science.aav9776