{"doi":"10.1016/j.celrep.2023.113636","title":"TDP-43-stratified single-cell proteomics of postmortem human spinal motor neurons reveals protein dynamics in amyotrophic lateral sclerosis","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.","journal":"Cell Reports","year":2024,"id":418230,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":53,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9285,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":240295,"name":"Santosh A. Misal","orcid":"0000-0002-8835-0130","position":1,"is_corresponding":false},{"id":482257,"name":"Richard H. Carson","orcid":null,"position":2,"is_corresponding":false},{"id":449348,"name":"J Chu","orcid":"0000-0001-7179-9428","position":3,"is_corresponding":false},{"id":138880,"name":"Hannah Boekweg","orcid":null,"position":4,"is_corresponding":false},{"id":1206582,"name":"Daisha Van Der Watt","orcid":null,"position":5,"is_corresponding":false},{"id":926756,"name":"Nora C. Welsh","orcid":"0000-0001-9313-4347","position":6,"is_corresponding":false},{"id":240297,"name":"Thy Truong","orcid":"0000-0002-6675-7685","position":7,"is_corresponding":false},{"id":240296,"name":"Yiran Liang","orcid":"0000-0002-8071-9984","position":8,"is_corresponding":false},{"id":1206583,"name":"Shanqin Xu","orcid":null,"position":9,"is_corresponding":false},{"id":647259,"name":"Gina Benedetto","orcid":null,"position":10,"is_corresponding":false},{"id":877008,"name":"Jake Gagnon","orcid":null,"position":11,"is_corresponding":false},{"id":44662,"name":"Samuel H. Payne","orcid":"0000-0002-8351-1994","position":12,"is_corresponding":false},{"id":240299,"name":"Edward D. Plowey","orcid":"0000-0001-9016-4751","position":13,"is_corresponding":false},{"id":138882,"name":"Ryan T. Kelly","orcid":"0000-0002-3339-4443","position":14,"is_corresponding":false},{"id":109109,"name":"Amanda J. Guise","orcid":"0000-0003-1124-9373","position":0,"is_corresponding":true}],"reference_count":106,"raw_metadata":null,"created_at":"2026-07-19T01:57:02.483590Z","pmid":"38183652","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}