Evidence map›Paper›PMID 42335888›Full record

ArticleCell2026

An emergent disease-associated motor neuron state precedes cell death in ALS.

Olivia Gautier, Jacob A Blum, Thao P Nguyen, Shaolong Cao, Sandy Klemm, Mai Yamakawa, Dann Huh, Jessica A Hurt, Nasa Sinnott-Armstrong, Yi Zeng and 16 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. A consensus spinal cord cell type atlas across mouse, macaque, and human.bioRxiv : the preprint server for biology · 2026
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

26 authors.

Olivia GautierDepartment of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Neurosciences Graduate Program, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: ogautier@stanford.edu.
Jacob A BlumDepartment of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Thao P NguyenDepartment of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Shaolong CaoResearch, Biogen Inc., Cambridge, MA 02142, USA.
Sandy KlemmDepartment of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Mai YamakawaProgram in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Dann HuhResearch, Biogen Inc., Cambridge, MA 02142, USA.
Jessica A HurtResearch, Biogen Inc., Cambridge, MA 02142, USA.
Nasa Sinnott-ArmstrongHerbold Computational Biology Program, Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA 98195, USA; Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA; Brotman Baty Institute, University of Washington, Seattle, WA 98195, USA.
Yi ZengDepartment of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA; Biohub - San Francisco, San Francisco, CA 94158, USA.
Chung-Ha O DavisDepartment of Neurobiology, Stanford University, Stanford, CA 94305, USA.
Juliane BomboschDepartment of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Chang LiuDepartment of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Lisa N EncarnacionDepartment of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Kevin A GuttenplanVollum Institute, Oregon Health and Sciences University, Portland, OR 97239, USA.
Derek ChenDepartment of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Arwa KathiriaDepartment of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Luke ZhaoDepartment of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Stephen MooreDepartments of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Alex MengDepartment of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA.
Kailee OngDepartment of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA.
Don W ClevelandDepartments of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
John RavitsDepartment of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA.
Jessica E RexachProgram in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
William J GreenleafDepartment of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Applied Physics, Stanford University, Stanford, CA 94305, USA; Biohub - San Francisco, San Francisco, CA 94158, USA.
Aaron D GitlerDepartment of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA; Biohub - San Francisco, San Francisco, CA 94158, USA; The Phil and Penny Knight Initiative for Brain Resilience, Stanford University, Stanford, CA 94305, USA. Electronic address: agitler@stanford.edu.

Funding

Technology to understand genetic variant effects in contextRM1HG010461 · NHGRI · UNIVERSITY OF WASHINGTON · PI Douglas M Fowler, Bruce Colston Trapnell · 2019 to 2026
$18.9M
Investigating regional and cellular vulnerabilities to tau pathology in young-onset Alzheimer's diseaseR01AG075802 · NIA · MAYO CLINIC JACKSONVILLE · PI BERNARDINO Francesco GHETTI, Lea Tenenholz Grinberg · 2022 to 2026
$15.5M
Human Biomarkers CoreU54NS123743 · NINDS · STANFORD UNIVERSITY · PI GITLER, AARON D. · 2021 to 2025
$8.2M
Role of central and peripheral immune crosstalk in FTD-Grn neurodegenerationRF1NS128800 · NINDS · UNIVERSITY OF FLORIDA · PI FINKBEINER, STEVEN M, TANSEY, MARIA DE LOURDES GAMEZ · 2022 to 2022
$2.4M
Defining and perturbing gene regulatory dynamics in the developing human brainR01NS128028 · NINDS · STANFORD UNIVERSITY · PI William James Greenleaf · 2023 to 2026
$2.4M
Defining modifiers and mechanisms of RAN translationR01AG064690 · NIA · STANFORD UNIVERSITY · PI Aaron D. Gitler, JOSEPH D PUGLISI · 2024 to 2026
$2.3M
Innovating next generation technologies to define mechanisms of neurodegenerative disease and devise therapeutic strategiesR35NS137159 · NINDS · STANFORD UNIVERSITY · PI Aaron D. Gitler · 2025 to 2026
$2.3M
Four Laser, 18 Color Cell Sorter in the SSFFS10RR025518 · NCRR · STANFORD UNIVERSITY · PI HERZENBERG, LEONARD A · 2009 to 2009
$500k
NCRR NIH HHS S10 RR025518NHGRI NIH HHS RM1 HG010461NIA NIH HHS R01 AG064690NIA NIH HHS R01 AG075802NINDS NIH HHS R01 NS128028NINDS NIH HHS R35 NS137159NINDS NIH HHS RF1 NS128800NINDS NIH HHS U54 NS123743
6 · The paper itself

Abstract

To define molecular determinants of motor neuron degeneration in amyotrophic lateral sclerosis (ALS), we generated longitudinal single-nucleus transcriptomes and chromatin accessibility profiles of spinal motor neurons together with spatial transcriptomics from the SOD1-G93A mouse model. Vulnerable alpha motor neurons showed thousands of molecular changes, marking a transition into a distinct cell state we named "disease-associated motor neurons" (DMs). We identified transcription factor networks that govern how healthy cells transition into DMs and those associated with motor neuron subtype-selective vulnerability. Upregulation of DM-associated transcription factors in human motor neurons induced key features of DMs, demonstrating an active regulatory component. Human ALS spinal cord single-nucleus RNA sequencing data demonstrated conservation of the DM signature in alpha motor neurons, and human orthologs of regions differentially accessible in SOD1-G93A mouse motor neurons were enriched for ALS genetic risk variants. Together, these findings establish a conserved, genetically linked motor neuron signature in ALS.

Indexed as

Amyotrophic Lateral SclerosisMotor NeuronsAnimalsCell DeathDisease Models, AnimalFemaleHumansMaleMiceMice, TransgenicSpinal CordSuperoxide Dismutase-1Transcription FactorsTranscriptomeSuperoxide Dismutase-1Transcription FactorsALScell statesmicroglial activationmotor neuronneurodegenerationselective vulnerabilitysnATAC-seqsnRNA-seqspatial transcriptomicsspinal cord

Identifiers

PMID42335888
PMCPMC13446465

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.