{"doi":"10.1101/2024.06.28.601266","title":"Human-specific paralogs of SRGAP2 induce neotenic features of microglia structural and functional maturation","abstract":"SUMMARY Microglia play key roles in shaping synaptic connectivity during neural circuits development. Whether microglia display human-specific features of structural and functional maturation is currently unknown. We show that the ancestral gene SRGAP2A and its human-specific (HS) paralogs SRGAP2B/C are not only expressed in cortical neurons but are the only HS gene duplications expressed in human microglia. Here, using combination of xenotransplantation of human induced pluripotent stem cell (hiPSC)-derived microglia and mouse genetic models, we demonstrate that (1) HS SRGAP2B/C are necessary and sufficient to induce neotenic features of microglia structural and functional maturation in a cell-autonomous manner, and (2) induction of SRGAP2-dependent neotenic features of microglia maturation non-cell autonomously impacts synaptic development in cortical pyramidal neurons. Our results reveal that, during human brain evolution, human-specific genes SRGAP2B/C coordinated the emergence of neotenic features of synaptic development by acting as genetic modifiers of both neurons and microglia.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":485614,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9472,"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":977630,"name":"Marine Krzisch","orcid":"0000-0002-9964-7992","position":1,"is_corresponding":false},{"id":1041540,"name":"Juyoun Yoo","orcid":"0000-0002-4600-7094","position":2,"is_corresponding":false},{"id":581317,"name":"Patricia R. Nano","orcid":"0000-0002-5507-2656","position":3,"is_corresponding":false},{"id":104403,"name":"Aparna Bhaduri","orcid":"0000-0003-4625-6899","position":4,"is_corresponding":false},{"id":30028,"name":"Rudolf Jaenisch","orcid":"0000-0002-2540-7099","position":5,"is_corresponding":false},{"id":187364,"name":"Franck Polleux","orcid":"0000-0003-4313-0481","position":6,"is_corresponding":false},{"id":1329120,"name":"Carlos Diaz-Salazar","orcid":null,"position":0,"is_corresponding":true}],"reference_count":84,"raw_metadata":null,"created_at":"2026-07-19T02:07:52.536246Z","pmid":"38979266","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":[]}