{"doi":"10.1101/2025.10.17.682973","title":"Radial-glia-to-astrocyte trans-differentiation and astrocyte transcriptional convergence are coordinated by CEH-43/DLX in <i>C. elegans</i>","abstract":"Abstract Mammalian radial glia can remodel to become astrocytes, which acquire common transcriptional states despite spatially and lineally distinct origins. To uncover molecular programs driving convergent radial-glia-to-astrocyte transformation, we investigated development of C. elegans CEPsh astrocytes, which also arise from distinct progenitors without cell division. Using lineage-restricted single-cell RNA sequencing, we delineate a two-phase program for CEPsh astrocyte formation. Transcriptionally disparate nascent CEPsh glia rapidly acquire a common radial-glia-like state, facilitating nerve ring (brain) assembly. Subsequently, convergent CEPsh glia upregulate astrocyte-specific gene expression. Both phases require the distal-less transcription factor CEH-43, expressed in CEPsh glia and their progenitors. CEH-43 binds conserved astrocyte-expressed genes, cell-autonomously activating both early and late CEPsh glia-specific gene expression. CEH-43 misexpression is sufficient to induce CEPsh astrocyte reporter expression. We demonstrate that CEH-43 homologs, DLX1/2, are expressed in mouse astrocytes, and comparative transcriptomics reveal additional parallels. Our findings provide a molecular foundation for understanding cell-division-independent radial-glia-to-astrocyte transformation.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":578406,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9524,"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":422745,"name":"Kenneth A. Bradley","orcid":"0000-0002-4757-5122","position":1,"is_corresponding":false},{"id":1488022,"name":"Jinghong J. Tang","orcid":"0009-0005-6875-4057","position":2,"is_corresponding":false},{"id":727819,"name":"Yoon A. Kim","orcid":null,"position":3,"is_corresponding":false},{"id":1164530,"name":"Ana Milosevic","orcid":"0000-0001-8200-626X","position":4,"is_corresponding":false},{"id":233475,"name":"Shai Shaham","orcid":"0000-0002-3751-975X","position":5,"is_corresponding":false},{"id":1488021,"name":"Simin Liu","orcid":"0000-0001-5181-5179","position":0,"is_corresponding":true}],"reference_count":149,"raw_metadata":null,"created_at":"2026-07-19T02:58:20.638044Z","pmid":"41279325","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":[]}