{"doi":"10.1371/journal.pgen.1010952","title":"Neurodevelopmental deficits and cell-type-specific transcriptomic perturbations in a mouse model of HNRNPU haploinsufficiency","abstract":"Heterozygous de novo loss-of-function mutations in the gene expression regulator HNRNPU cause an early-onset developmental and epileptic encephalopathy. To gain insight into pathological mechanisms and lay the potential groundwork for developing targeted therapies, we characterized the neurophysiologic and cell-type-specific transcriptomic consequences of a mouse model of HNRNPU haploinsufficiency. Heterozygous mutants demonstrated global developmental delay, impaired ultrasonic vocalizations, cognitive dysfunction and increased seizure susceptibility, thus modeling aspects of the human disease. Single-cell RNA-sequencing of hippocampal and neocortical cells revealed widespread, yet modest, dysregulation of gene expression across mutant neuronal subtypes. We observed an increased burden of differentially-expressed genes in mutant excitatory neurons of the subiculum-a region of the hippocampus implicated in temporal lobe epilepsy. Evaluation of transcriptomic signature reversal as a therapeutic strategy highlights the potential importance of generating cell-type-specific signatures. Overall, this work provides insight into HNRNPU-mediated disease mechanisms and provides a framework for using single-cell RNA-sequencing to study transcriptional regulators implicated in disease.","journal":"PLoS Genetics","year":2023,"id":332931,"datarank":0.48283137373023016,"base_score":3.2188758248682006,"endowment":3.2188758248682006,"self_citation_contribution":0.48283137373023016,"citation_network_contribution":0.0,"self_endowment_contribution":0.48283137373023016,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":24,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9461,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":40851,"name":"Ryan S. Dhindsa","orcid":"0000-0002-8965-0813","position":1,"is_corresponding":false},{"id":1059618,"name":"Gabriela Louise de Almeida Sampaio","orcid":"0000-0002-9955-258X","position":2,"is_corresponding":false},{"id":558700,"name":"Andrew K. Ressler","orcid":"0000-0001-5481-2774","position":3,"is_corresponding":false},{"id":559755,"name":"Elizabeth E. Rafikian","orcid":null,"position":4,"is_corresponding":false},{"id":290330,"name":"Sabrina Petri","orcid":null,"position":5,"is_corresponding":false},{"id":559756,"name":"Verity A. Letts","orcid":null,"position":6,"is_corresponding":false},{"id":295021,"name":"Jia Jie Teoh","orcid":"0000-0001-7100-5763","position":7,"is_corresponding":false},{"id":104467,"name":"Junqiang Ye","orcid":"0000-0002-4529-0713","position":8,"is_corresponding":false},{"id":288717,"name":"Sophie Colombo","orcid":"0000-0001-8945-5631","position":9,"is_corresponding":false},{"id":288724,"name":"Yueqing Peng","orcid":"0000-0002-3488-0670","position":10,"is_corresponding":false},{"id":558701,"name":"Mu Yang","orcid":"0000-0001-7084-029X","position":11,"is_corresponding":false},{"id":288726,"name":"Michael J. Boland","orcid":"0000-0001-5649-9603","position":12,"is_corresponding":false},{"id":96540,"name":"Wayne N. Frankel","orcid":"0000-0003-2241-5314","position":13,"is_corresponding":false},{"id":30756,"name":"David B. Goldstein","orcid":"0000-0002-1111-2820","position":14,"is_corresponding":false},{"id":558699,"name":"Sarah A. Dugger","orcid":"0000-0002-8005-6754","position":0,"is_corresponding":true}],"reference_count":92,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:09:35.125543Z","pmid":"37782669","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":[]}