{"doi":"10.1038/s41467-025-56590-7","title":"Phospho-seq: integrated, multi-modal profiling of intracellular protein dynamics in single cells","abstract":"Cell signaling plays a critical role in neurodevelopment, regulating cellular behavior and fate. While multimodal single-cell sequencing technologies are rapidly advancing, scalable and flexible profiling of cell signaling states alongside other molecular modalities remains challenging. Here we present Phospho-seq, an integrated approach that aims to quantify cytoplasmic and nuclear proteins, including those with post-translational modifications, and to connect their activity with cis-regulatory elements and transcriptional targets. We utilize a simplified benchtop antibody conjugation method to create large custom neuro-focused antibody panels for simultaneous protein and scATAC-seq profiling on whole cells, alongside both experimental and computational strategies to incorporate transcriptomic measurements. We apply our workflow to cell lines, induced pluripotent stem cells, and months-old retinal and brain organoids to demonstrate its broad applicability. We show that Phospho-seq can provide insights into cellular states and trajectories, shed light on gene regulatory relationships, and help explore the causes and effects of diverse cell signaling in neurodevelopment.","journal":"Nature Communications","year":2025,"id":517831,"datarank":0.33077916256608686,"base_score":2.0794415416798357,"endowment":2.0794415416798357,"self_citation_contribution":0.31191623125197543,"citation_network_contribution":0.018862931314111413,"self_endowment_contribution":0.31191623125197543,"citer_contribution":0.018862931314111413,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":4,"citers_with_citation_signal":2,"citers_with_endowment":2,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9283,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":537825,"name":"Austin Hartman","orcid":"0000-0001-7278-1852","position":1,"is_corresponding":false},{"id":628640,"name":"Fides Zenk","orcid":"0000-0002-0324-0902","position":2,"is_corresponding":false},{"id":55388,"name":"Philipp Wahle","orcid":"0000-0002-4728-806X","position":3,"is_corresponding":false},{"id":642626,"name":"Giovanna Brancati","orcid":"0000-0002-8589-3463","position":4,"is_corresponding":false},{"id":956679,"name":"Carol Dalgarno","orcid":"0000-0002-2237-034X","position":5,"is_corresponding":false},{"id":29636,"name":"Barbara Treutlein","orcid":"0000-0002-3299-5597","position":6,"is_corresponding":false},{"id":311859,"name":"Rahul Satija","orcid":"0000-0001-9448-8833","position":7,"is_corresponding":false},{"id":1028481,"name":"John D. Blair","orcid":"0000-0001-7517-6148","position":0,"is_corresponding":true}],"reference_count":91,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:49:04.756302Z","pmid":"39905064","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":[]}