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In addition, while the niche environment in the bone marrow minimally affects myeloid-biased hematopoiesis, aged thymi and spleens substantially hinder lymphoid hematopoiesis, resulting in further myeloid domination. Thus, we demonstrate that myeloid-biased hematopoiesis in aged mice originates due to alteration of the ratio between LT-HSCs and ST-HSCs rather than in heterogeneous HSC clones with various cell fates.</jats:p>","journal":"eLife","year":2025,"id":599414,"datarank":0.16479184330021646,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.0,"self_endowment_contribution":0.16479184330021646,"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":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":1536207,"name":"Taro Sakamaki","orcid":null,"position":1,"is_corresponding":false},{"id":1536208,"name":"Akiomi Nagasaka","orcid":null,"position":2,"is_corresponding":false},{"id":1536209,"name":"Kevin Shuolong Kao","orcid":null,"position":3,"is_corresponding":false},{"id":1536210,"name":"Kay Sadaoka","orcid":null,"position":4,"is_corresponding":false},{"id":1536211,"name":"Masahide Asano","orcid":null,"position":5,"is_corresponding":false},{"id":1272916,"name":"Nobuyuki Yamamoto","orcid":"0000-0001-9169-8106","position":6,"is_corresponding":false},{"id":374971,"name":"Akifumi Takaori‐Kondo","orcid":"0000-0001-7678-4284","position":7,"is_corresponding":false},{"id":1234284,"name":"Masanori Miyanishi","orcid":"0000-0002-0527-3652","position":8,"is_corresponding":false},{"id":1536206,"name":"Katsuyuki Nishi","orcid":"0009-0009-4296-7619","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Alteration of long- and short-term hematopoietic stem cell ratio causes myeloid-biased hematopoiesis","abstract":"<jats:p>Myeloid-biased hematopoiesis is a well-known age-related alteration. Several possibilities, including myeloid-biased hematopoietic stem cell (HSC) clones, may explain this. However, the precise mechanisms remain controversial. Utilizing the Hoxb5 reporter system to prospectively isolate long-term HSCs (LT-HSCs) and short-term HSCs (ST-HSCs), we found that young and aged LT-HSCs co-transplanted into the same recipients demonstrated nearly equivalent myeloid lineage output, contrary to the theory of myeloid-biased HSC clones. Transcriptomics indicated no significant myeloid gene enrichment in aged LT-HSCs compared to their young counterparts. Instead, transplanting reconstituted young HSCs with the ratio of LT/ST-HSCs seen in aged mice can significantly skew the lineage output to myeloid cells. In addition, while the niche environment in the bone marrow minimally affects myeloid-biased hematopoiesis, aged thymi and spleens substantially hinder lymphoid hematopoiesis, resulting in further myeloid domination. 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