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Science. 2019 Apr 5;364(6435):89-93. doi: 10.1126/science.aav9776.

Spatiotemporal dynamics of molecular pathology in amyotrophic lateral sclerosis.

Author information

1
Center for Genomics of Neurodegenerative Disease, New York Genome Center, New York, NY, USA.
2
Center for Computational Biology, Flatiron Institute, New York, NY, USA.
3
Broad Institute of MIT and Harvard, Cambridge, MA, USA.
4
Science for Life Laboratory, Department of Gene Technology, KTH Royal Institute of Technology, Stockholm, Sweden.
5
Mortimer B. Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY, USA.
6
Science for Life Laboratory, Department of Gene Technology, KTH Royal Institute of Technology, Stockholm, Sweden. hphatnani@nygenome.org rb133@nyu.edu joakim.lundeberg@scilifelab.se.
7
Department of Bioengineering, Stanford University, Stanford, CA, USA.
8
Center for Computational Biology, Flatiron Institute, New York, NY, USA. hphatnani@nygenome.org rb133@nyu.edu joakim.lundeberg@scilifelab.se.
9
Center for Data Science, New York University, New York, NY, USA.
10
Center for Genomics of Neurodegenerative Disease, New York Genome Center, New York, NY, USA. hphatnani@nygenome.org rb133@nyu.edu joakim.lundeberg@scilifelab.se.
#
Contributed equally

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.

PMID:
30948552
DOI:
10.1126/science.aav9776
[Indexed for MEDLINE]

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