Evidence map›Paper›PMID 38183652›Full record

ArticleCell reports2024

TDP-43-stratified single-cell proteomics of postmortem human spinal motor neurons reveals protein dynamics in amyotrophic lateral sclerosis.

Amanda J Guise, Santosh A Misal, Richard Carson, Jen-Hwa Chu, Hannah Boekweg, Daisha Van Der Watt, Nora C Welsh, Thy Truong, Yiran Liang, Shanqin Xu and 5 more

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed
17.0field-weighted citation impact, top 1% of its field
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

39 citing papers in PubMed, 48 citations in OpenAlex.

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  8. Decoding neurodegeneration one cell at a time.The Journal of clinical investigation · 2026
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 2 institutions in 1 country.

Amanda J GuiseBiogen, Inc., Cambridge, MA 02142, USA.
Santosh A MisalDepartment of Chemistry and Biochemistry, Brigham Young University, Provo, UT 84602, USA.
Richard CarsonDepartment of Chemistry and Biochemistry, Brigham Young University, Provo, UT 84602, USA.
Jen-Hwa ChuBiogen, Inc., Cambridge, MA 02142, USA.
Hannah BoekwegBiology Department, Brigham Young University, Provo, UT 84602, USA.
Daisha Van Der WattBiology Department, Brigham Young University, Provo, UT 84602, USA.
Nora C WelshBiogen, Inc., Cambridge, MA 02142, USA.
Thy TruongDepartment of Chemistry and Biochemistry, Brigham Young University, Provo, UT 84602, USA.
Yiran LiangDepartment of Chemistry and Biochemistry, Brigham Young University, Provo, UT 84602, USA.
Shanqin XuBiogen, Inc., Cambridge, MA 02142, USA.
Gina BenedettoBiogen, Inc., Cambridge, MA 02142, USA.
Jake GagnonBiogen, Inc., Cambridge, MA 02142, USA.
Samuel H PayneBiology Department, Brigham Young University, Provo, UT 84602, USA.
Edward D PloweyBiogen, Inc., Cambridge, MA 02142, USA. Electronic address: ed.plowey@biogen.com.
Ryan T KellyDepartment of Chemistry and Biochemistry, Brigham Young University, Provo, UT 84602, USA. Electronic address: ryan.kelly@byu.edu.
Brigham Young University · USBiogen (United States) · US

Funding

Area A: In-Depth Proteome Mapping of the Tumor Microenvironment with Single-Cell ResolutionR33CA225248 · NCI · BRIGHAM YOUNG UNIVERSITY · PI KELLY, RYAN T · 2017 to 2017
$1.7M
Fully automated and ultra-high-throughput platform for in-depth single-cell proteomicsR01GM138931 · NIGMS · BRIGHAM YOUNG UNIVERSITY · PI KELLY, RYAN T · 2020 to 2023
$1.6M
NCI NIH HHS R33 CA225248NIGMS NIH HHS R01 GM138931
6 · The paper itself

Abstract

A limitation of conventional bulk-tissue proteome studies in amyotrophic lateral sclerosis (ALS) is the confounding of motor neuron (MN) signals by admixed non-MN proteins. Here, we leverage laser capture microdissection and nanoPOTS single-cell mass spectrometry-based proteomics to query changes in protein expression in single MNs from postmortem ALS and control tissues. In a follow-up analysis, we examine the impact of stratification of MNs based on cytoplasmic transactive response DNA-binding protein 43 (TDP-43)+ inclusion pathology on the profiles of 2,238 proteins. We report extensive overlap in differentially abundant proteins identified in ALS MNs with or without overt TDP-43 pathology, suggesting early and sustained dysregulation of cellular respiration, mRNA splicing, translation, and vesicular transport in ALS. Together, these data provide insights into proteome-level changes associated with TDP-43 proteinopathy and begin to demonstrate the utility of pathology-stratified trace sample proteomics for understanding single-cell protein dynamics in human neurologic diseases.

Indexed as

Amyotrophic Lateral SclerosisDNA-Binding ProteinsHumansMotor NeuronsProteomeProteomicsDNA-Binding ProteinsProteomeTARDBP protein, humanALSCP: Molecular biologyCP: Neurosciencelaser capturemotor neuronnanoPOTSretromersingle-cell proteomicsSTMN2TDP-43 proteinopathy

Identifiers

PMID38183652
PMCPMC10926001
OpenAlexW4390603573

What OpenQuestion holds

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LicenceCC BY-NC-ND
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.