Spatiotemporal dynamics of molecular pathology in amyotrophic lateral sclerosis

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 proc...

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Published in:Science (American Association for the Advancement of Science) 2019-04, Vol.364 (6435), p.89-93
Main Authors: Maniatis, Silas, Äijö, Tarmo, Vickovic, Sanja, Braine, Catherine, Kang, Kristy, Mollbrink, Annelie, Fagegaltier, Delphine, Andrusivová, Žaneta, Saarenpää, Sami, Saiz-Castro, Gonzalo, Cuevas, Miguel, Watters, Aaron, Lundeberg, Joakim, Bonneau, Richard, Phatnani, Hemali
Format: Article
Language:English
Subjects:
Amyotrophic lateral sclerosis
Amyotrophic Lateral Sclerosis - genetics
Amyotrophic Lateral Sclerosis - pathology
Animal models
Animals
Astrocytes - metabolism
Astrocytes - pathology
Autopsy
Brain
Degeneration
Denervation
Disease Models, Animal
Gene Expression
Gene Expression Profiling
Gene sequencing
Humans
Mice
Microglia
Microglia - metabolism
Microglia - pathology
Molecular modelling
Motor neuron diseases
Motor Neurons - metabolism
Motor Neurons - pathology
Motors
Muscle, Skeletal - pathology
Muscle, Skeletal - physiopathology
Muscles
Nerve Degeneration - genetics
Nerve Degeneration - physiopathology
Neurodegeneration
Neuroglia - metabolism
Neuroglia - pathology
Neuronal-glial interactions
Paralysis
Postmortem Changes
Ribonucleic acid
RNA
Skeletal muscle
Spatio-Temporal Analysis
Spinal cord
Spinal Cord - metabolism
Spinal Cord - pathology
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Description
Summary: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.
ISSN:0036-8075
1095-9203
1095-9203
DOI:10.1126/science.aav9776