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Spatiotemporal dynamics of molecular pathology in amyotrophic lateral sclerosis
Open accessPublished version of a preprint
Abstract
Spatiotemporal gene expression in ALS: Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease that affects nerve cells in the brain and the spinal cord. It has proven difficult to identify the early stages of disease and where it spreads within the body. Maniatis et al. used RNA sequencing to define transcriptomic changes over the course of disease in different regions of the spinal cord of a mouse ALS model and a postmortem human ALS spinal cord. From changes in gene expression, they identified disease-associated pathways and established the key steps in motor neuron degeneration observed in ALS. Science , this issue p. 89
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“Statistical methods that failed to account for variability between biological replicates identified thousands of DE genes within each region (Fig. 4f and Supplementary Fig. 6e).”
From Confronting false discoveries in single-cell differential expression (2021) · cites this paper as [24]
In the citing paper
“Maniatis et al. provided a comprehensive characterization of transcriptional changes in spinal cords of an ALS mouse model and patients.”
From Spatial Transcriptomics and In Situ Sequencing to Study Alzheimer’s Disease (2020) · cites this paper as Maniatis et al., 2019
In the citing paper
“the dysregulation of module 8 can be rescued by ablation of autophagy in neurons in Atg7 cKO mice (Maniatis et al., 2019).”
From Spatial Transcriptomics and In Situ Sequencing to Study Alzheimer’s Disease (2020) · cites this paper as Maniatis et al., 2019
In the citing paper
“The co-expression networks are cell-type-annotated at the level of submodule levels.”
From Spatial Transcriptomics and In Situ Sequencing to Study Alzheimer’s Disease (2020) · cites this paper as Maniatis et al., 2019
In the citing paper
“Finally, we compared all marker genes that we highlight in this paper (those in Table 1 and all figures) to their patterns in a recent spatial transcriptomics analysis of the spinal cord28 and to the Allen29 and Gensat30 expression databases and found general concordance between these resources (Supplementary Table 4).”
From A harmonized atlas of mouse spinal cord cell types and their spatial organization (2021) · cites this paper as [28]
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Metadata
- Authors
- 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.
- Affiliations
- New York Genome Center (US)
- Flatiron Institute (US)
- Center for Genomics of Neurodegenerative Disease, New York Genome Center, New York, NY, USA.
- Science for Life Laboratory (SE)
- Mortimer B. Zuckerman Mind Brain Behavior Institute (US)
- Corresponding author
- Lundeberg, Joakim
- Bonneau, Richard
- Phatnani, Hemali
- ORCID
- Venue
- Science
- Published
- 2019-04-05
- Volume
- 364
- Issue
- 6435
- Pages
- 89-93
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2952459265
- Cited by
- 429
- References
- 55
- Citations by year
- 2026: 38 · 2025: 62 · 2024: 56 · 2023: 58 · 2022: 76 · 2021: 74 · 2020: 50 · 2019: 13
- FWCI
- 36.20
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Science (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Simons Foundation
- Target ALS
- Knut och Alice Wallenbergs Stiftelse (2016.0454)
- the ALS Association (15-LGCA-234)
- The Tow Foundation
- Topics
- Health Sciences › Medicine › Clinical Neurology › Amyotrophic Lateral Sclerosis Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- amyotrophic lateral sclerosis, motor neuron degeneration, spinal cord transcriptome, microglia, astrocytes, glial interactions, disease progression, gene expression dynamics, transcriptional pathways
- MeSH terms
- Amyotrophic Lateral Sclerosis, Animals, Astrocytes, Disease Models, Animal, Humans, Motor Neurons, Nerve Degeneration, Neuroglia, Postmortem Changes, Spinal Cord, Gene Expression, Microglia, Muscle, Skeletal, Gene Expression Profiling, Mice, Transcriptome, Spatio-Temporal Analysis
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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