{"doi":"10.1101/2024.06.13.597128","title":"Reverse engineering neuron type-specific and type-orthogonal splicing-regulatory networks using single-cell transcriptomes","abstract":"Cell type-specific alternative splicing (AS) enables differential gene isoform expression between diverse neuron types with distinct identities and functions. Current studies linking individual RNA-binding proteins (RBPs) to AS in a few neuron types underscore the need for holistic modeling. Here, we use network reverse engineering to derive a map of the neuron type-specific AS regulatory landscape from 133 mouse neocortical cell types defined by single-cell transcriptomes. This approach reliably inferred the regulons of 350 RBPs and their cell type-specific activities. Our analysis revealed driving factors delineating neuronal identities, among which we validated Elavl2 as a key RBP for MGE-specific splicing in GABAergic interneurons using an in vitro ESC differentiation system. We also identified a module of exons and candidate regulators specific for long- and short-projection neurons across multiple neuronal classes. This study provides a resource for elucidating splicing regulatory programs that drive neuronal molecular diversity, including those that do not align with gene expression-based classifications.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":487114,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9498,"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":105782,"name":"Melissa Campbell","orcid":"0000-0002-8358-7307","position":1,"is_corresponding":false},{"id":894838,"name":"Miquel Anglada-Girotto","orcid":"0000-0003-1885-8649","position":2,"is_corresponding":false},{"id":406988,"name":"Huijuan Feng","orcid":"0000-0002-4005-560X","position":3,"is_corresponding":false},{"id":19046,"name":"Andrea Califano","orcid":"0000-0003-4742-3679","position":4,"is_corresponding":false},{"id":706151,"name":"Edmund Au","orcid":"0000-0003-3190-9711","position":5,"is_corresponding":false},{"id":406994,"name":"Chaolin Zhang","orcid":"0000-0002-8310-7537","position":6,"is_corresponding":false},{"id":646605,"name":"Daniel F. Moakley","orcid":"0000-0002-3279-4189","position":0,"is_corresponding":true}],"reference_count":94,"raw_metadata":null,"created_at":"2026-07-19T02:08:06.013846Z","pmid":"38915499","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":[]}