{"doi":"10.1101/2024.11.13.623446","title":"Transient upregulation of procaspase-3 during oligodendrocyte fate decisions","abstract":"<jats:title>ABSTRACT</jats:title>\n                <jats:p>Oligodendrocytes are generated throughout life and in neurodegenerative conditions from brain resident oligodendrocyte precursor cells (OPCs). The transition from OPC to oligodendrocyte involves a complex cascade of molecular and morphological states that position the cell to make a fate decision to integrate as a myelinating oligodendrocyte or die through apoptosis. Oligodendrocyte maturation impacts the cell death mechanisms that occur in degenerative conditions, but it is unclear if and how the cell death machinery changes as OPCs transition into oligodendrocytes. Here, we discovered that differentiating oligodendrocytes transiently upregulate the zymogen procaspase-3, equipping these cells to make a survival decision during differentiation. Pharmacological inhibition of caspase-3 decreases oligodendrocyte density, indicating that procaspase-3 upregulation promotes differentiation. Moreover, using procaspase-3 as a marker, we show that oligodendrocyte differentiation continues in the aging cortex and white matter. Taken together, our data establish procaspase-3 as a differentiating oligodendrocyte marker and provide insight into the underlying mechanisms occurring during the decision to integrate or die.</jats:p>","journal":null,"year":null,"id":614566,"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":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":586805,"name":"Timothy W. Chapman","orcid":"0000-0001-6303-1080","position":1,"is_corresponding":false},{"id":1168184,"name":"Enrique T. Piedra","orcid":null,"position":2,"is_corresponding":false},{"id":1583714,"name":"Matthew E. Ciolkowski","orcid":null,"position":3,"is_corresponding":false},{"id":334004,"name":"Robert Hill","orcid":"0000-0001-6080-8712","position":4,"is_corresponding":false},{"id":1583713,"name":"Yasmine Kamen","orcid":"0000-0003-1867-7397","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Transient upregulation of procaspase-3 during oligodendrocyte fate decisions","abstract":"<jats:title>ABSTRACT</jats:title>\n                <jats:p>Oligodendrocytes are generated throughout life and in neurodegenerative conditions from brain resident oligodendrocyte precursor cells (OPCs). The transition from OPC to oligodendrocyte involves a complex cascade of molecular and morphological states that position the cell to make a fate decision to integrate as a myelinating oligodendrocyte or die through apoptosis. Oligodendrocyte maturation impacts the cell death mechanisms that occur in degenerative conditions, but it is unclear if and how the cell death machinery changes as OPCs transition into oligodendrocytes. Here, we discovered that differentiating oligodendrocytes transiently upregulate the zymogen procaspase-3, equipping these cells to make a survival decision during differentiation. Pharmacological inhibition of caspase-3 decreases oligodendrocyte density, indicating that procaspase-3 upregulation promotes differentiation. Moreover, using procaspase-3 as a marker, we show that oligodendrocyte differentiation continues in the aging cortex and white matter. Taken together, our data establish procaspase-3 as a differentiating oligodendrocyte marker and provide insight into the underlying mechanisms occurring during the decision to integrate or die.</jats:p>","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"39605489","pmcid":null,"openalex_id":"https://openalex.org/W4404428752","authors":[],"funders":[{"funder_name":"National Institutes of Health","grant_id":"5R01NS122800-04","title":"Glial Mechanisms Governing the Removal and Repair of Degenerating Myelin"},{"funder_name":"NINDS NIH HHS","grant_id":"R01 NS122800","title":null}],"total_grants":2,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"green","license":"cc-by-nc-nd","oa_locations":[{"url":"https://www.biorxiv.org/content/biorxiv/early/2024/11/14/2024.11.13.623446.full.pdf","host_type":"repository"},{"url":"https://www.biorxiv.org/content/biorxiv/early/2024/11/14/2024.11.13.623446.full.pdf","host_type":"repository"},{"url":"https://syndication.highwire.org/content/doi/10.1101/2024.11.13.623446","host_type":"publisher"},{"url":"https://doi.org/10.1101/2024.11.13.623446","host_type":"repository"},{"url":"https://pubmed.ncbi.nlm.nih.gov/39605489","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/11601457","host_type":"repository"},{"url":"https://doi.org/10.1523/jneurosci.2066-24.2025","host_type":""},{"url":"https://pubmed.ncbi.nlm.nih.gov/39837665","host_type":""},{"url":"http://dx.doi.org/10.1101/2024.11.13.623446","host_type":""},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11924999/","host_type":""},{"url":"https://pubmed.ncbi.nlm.nih.gov/39837665/","host_type":""},{"url":"https://doi.org/10.1523/JNEUROSCI.2066-24.2025","host_type":""}],"fields_of_study":["Neurogenesis and neuroplasticity mechanisms","Neuroscience and Neuropharmacology Research","Neuroinflammation and Neurodegeneration Mechanisms","0301 basic medicine","03 medical and health sciences"],"mesh_terms":[],"keywords":["Oligodendrocyte","Downregulation and upregulation","Cell biology","Biology","Programmed cell death","Apoptosis","Neuroscience","Myelin","Biochemistry","Central nervous system","Gene","Male","Oligodendrocyte Precursor Cells","Caspase 3","Cell Differentiation","Article","Up-Regulation","Mice, Inbred C57BL","Oligodendroglia","Mice","Animals","Female","Research Articles"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Peace, Justice and strong institutions"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-02T14:22:13.982813Z","pmid":null,"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":[]}