{"doi":"10.1093/stmcls/sxaf047","title":"15-PGDH inhibition enhances hematopoietic regeneration during aging","abstract":"Hematopoietic aging is characterized by diminished stem cell regenerative capacity and an increased risk of hematologic dysfunction. We previously identified that the prostaglandin-degrading enzyme 15-hydroxyprostaglandin dehydrogenase (15-PGDH) regulates hematopoietic stem cell (HSC) activity. Here, we expand on this work and demonstrate that in aged mice: (1) 15-PGDH expression and activity remain conserved in the bone marrow (BM) and spleen, suggesting that it remains a viable therapeutic target in aging; (2) prolonged PGDH inhibition (PGDHi) significantly increases the frequency and number of phenotypic hematopoietic stem and progenitor cells across multiple compartments, with transcriptional changes indicative of enhanced function; (3) PGDHi-treated BM enhances short-term hematopoietic recovery following transplantation, leading to improved peripheral blood output and accelerated multilineage reconstitution; and (4) PGDHi confers a competitive advantage in primary hematopoietic transplantation while mitigating age-associated myeloid bias in secondary transplants. Notably, these effects occur without perturbing steady-state blood production, suggesting that PGDHi enhances hematopoiesis under regenerative conditions while maintaining homeostasis. Our work identifies PGDHi as a translatable intervention to rejuvenate aged HSCs and mitigate hematopoietic decline.","journal":"Stem Cells","year":2025,"id":541685,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9608,"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":1283698,"name":"Brittany A Cordova","orcid":null,"position":1,"is_corresponding":false},{"id":1430436,"name":"Hong Ma","orcid":"0000-0001-6414-8870","position":2,"is_corresponding":false},{"id":1283697,"name":"Bailey R Klein","orcid":null,"position":3,"is_corresponding":false},{"id":1430877,"name":"Lyannah A Contreras","orcid":null,"position":4,"is_corresponding":false},{"id":1430878,"name":"Ritisha Rashmil","orcid":null,"position":5,"is_corresponding":false},{"id":1430879,"name":"Filip Goshevski","orcid":null,"position":6,"is_corresponding":false},{"id":1283696,"name":"Julianne N P Smith","orcid":null,"position":7,"is_corresponding":false},{"id":250435,"name":"Derek J. Taylor","orcid":"0000-0001-9932-1856","position":8,"is_corresponding":false},{"id":247916,"name":"Andrew A. Pieper","orcid":"0000-0001-6299-6577","position":9,"is_corresponding":false},{"id":2243,"name":"Sanford D. Markowitz","orcid":"0000-0001-5369-5254","position":10,"is_corresponding":false},{"id":488780,"name":"Amar Desai","orcid":"0000-0001-8649-6630","position":11,"is_corresponding":false},{"id":1283285,"name":"Rahul Chaudhary","orcid":"0009-0003-6183-9483","position":0,"is_corresponding":true}],"reference_count":46,"raw_metadata":null,"created_at":"2026-07-19T02:52:51.593043Z","pmid":"40608981","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":[]}