{"doi":"10.1016/j.celrep.2018.11.056","title":"Heterogeneous Responses of Hematopoietic Stem Cells to Inflammatory Stimuli Are Altered with Age","abstract":"Long-term hematopoietic stem cells (LT-HSCs) maintain hematopoietic output throughout an animal's lifespan. However, with age, the balance is disrupted, and LT-HSCs produce a myeloid-biased output, resulting in poor immune responses to infectious challenge and the development of myeloid leukemias. Here, we show that young and aged LT-HSCs respond differently to inflammatory stress, such that aged LT-HSCs produce a cell-intrinsic, myeloid-biased expression program. Using single-cell RNA sequencing (scRNA-seq), we identify a myeloid-biased subset within the LT-HSC population (mLT-HSCs) that is prevalent among aged LT-HSCs. We identify CD61 as a marker of mLT-HSCs and show that CD61-high LT-HSCs are uniquely primed to respond to acute inflammatory challenge. We predict that several transcription factors regulate the mLT-HSCs gene program and show that Klf5, Ikzf1, and Stat3 play an important role in age-related inflammatory myeloid bias. We have therefore identified and isolated an LT-HSC subset that regulates myeloid versus lymphoid balance under inflammatory challenge and with age.","journal":"Cell Reports","year":2018,"id":9564,"datarank":0.7909499337845621,"base_score":5.272999558563747,"endowment":5.272999558563747,"self_citation_contribution":0.7909499337845621,"citation_network_contribution":0.0,"self_endowment_contribution":0.7909499337845621,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":194,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.0459,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2018-12-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":396,"name":"Arnav Mehta","orcid":"0000-0002-0313-2848","position":1,"is_corresponding":false},{"id":3029,"name":"Carl G. de Boer","orcid":"0000-0001-8935-5921","position":2,"is_corresponding":false},{"id":2681,"name":"Monika S. Kowalczyk","orcid":"0000-0003-0525-9196","position":3,"is_corresponding":false},{"id":80034,"name":"Kevin Lee","orcid":"0000-0002-5606-8683","position":4,"is_corresponding":false},{"id":80035,"name":"Pearce Haldeman","orcid":"0000-0002-9667-4979","position":5,"is_corresponding":false},{"id":15888,"name":"Noga Rogel","orcid":null,"position":6,"is_corresponding":false},{"id":32738,"name":"Daneyal Farouq","orcid":null,"position":8,"is_corresponding":false},{"id":29633,"name":"Prisca Liberali","orcid":"0000-0003-0695-6081","position":9,"is_corresponding":false},{"id":6310,"name":"David Baltimore","orcid":"0000-0001-8723-8190","position":10,"is_corresponding":false},{"id":35377,"name":"Abigail Knecht","orcid":"0000-0003-1084-1623","position":11,"is_corresponding":false},{"id":6305,"name":"Mati Mann","orcid":null,"position":0,"is_corresponding":true}],"reference_count":70,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-03-01T18:20:47.508186Z","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":[]}