Evidence map›Paper›PMID 40909710›Full record

ArticlebioRxiv : the preprint server for biology2025

An emergent disease-associated motor neuron state precedes cell death in a mouse model of ALS.

Olivia Gautier, Jacob A Blum, Thao P Nguyen, Sandy Klemm, Mai Yamakawa, Nasa Sinnott-Armstrong, Yi Zeng, Chung-Ha O Davis, Juliane Bombosch, Lisa Nakayama and 7 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors.

Olivia GautierDepartment of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
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.
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.
Nasa Sinnott-ArmstrongHerbold Computational Biology Program, Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA 98195, USA.ORCID 0000-0003-4490-0601
Yi ZengDepartment of Genetics, Stanford University School of Medicine, Stanford, CA 94305, 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.
Lisa NakayamaDepartment 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 KathiraDepartment of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Luke ZhaoDepartment of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Jessica E RexachProgram in Neurogenetics, Department of Neurology, 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.
Aaron D GitlerDepartment of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.ORCID 0000-0001-8603-1526

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 uncover molecular determinants of motor neuron degeneration and selective vulnerability in amyotrophic lateral sclerosis (ALS), we generated longitudinal single-nucleus transcriptomes and chromatin accessibility profiles of spinal motor neurons from the SOD1-G93A ALS mouse model. Vulnerable alpha motor neurons showed thousands of molecular changes, marking a transition into a novel cell state we named 'disease-associated motor neurons' (DAMNs). We identified transcription factor regulatory networks that govern how healthy cells transition into DAMNs as well as those linked to vulnerable and resistant motor neuron subtypes. Using spatial transcriptomics, we found reactive glia located near motor neurons early in disease, suggesting early signaling events between motor neurons and glia. Finally, we found that the human orthologs of genomic regions with differential accessibility in SOD1-G93A alpha motor neurons are enriched for single nucleotide polymorphisms associated with human ALS, providing evidence that the genetic underpinnings of motor neuron vulnerability are conserved.

Identifiers

PMID40909710
PMCPMC12407787

What Socratic holds

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LicenceCC BY-NC
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 Socratic graph.