{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Kao YR"],"funding":["NIA NIH HHS","NIDDK NIH HHS","NHLBI NIH HHS","NCI NIH HHS","National Institutes of Health"],"pagination":["378-397.e12"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10939794"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["31(3)"],"pubmed_abstract":["Mechanisms governing the maintenance of blood-producing hematopoietic stem and multipotent progenitor cells (HSPCs) are incompletely understood, particularly those regulating fate, ensuring long-term maintenance, and preventing aging-associated stem cell dysfunction. We uncovered a role for transitory free cytoplasmic iron as a rheostat for adult stem cell fate control. We found that HSPCs harbor comparatively small amounts of free iron and show the activation of a conserved molecular response to limited iron-particularly during mitosis. To study the functional and molecular consequences of iron restriction, we developed models allowing for transient iron bioavailability limitation and combined single-molecule RNA quantification, metabolomics, and single-cell transcriptomic analyses with functional studies. Our data reveal that the activation of the limited iron response triggers coordinated metabolic and epigenetic events, establishing stemness-conferring gene regulation. Notably, we find that aging-associated cytoplasmic iron loading reversibly attenuates iron-dependent cell fate control, explicating intervention strategies for dysfunctional aged stem cells."],"journal":["Cell stem cell"],"pubmed_title":["An iron rheostat controls hematopoietic stem cell fate."],"pmcid":["PMC10939794"],"funding_grant_id":["R35 CA253127","P30 CA013330","T32 AG023475","R01 DK123327","R01 CA230756","RF1 AG043517","R01 HL146442","K00 CA223044","R01 HL148151","R01 HL157948"],"pubmed_authors":["D'Alessandro A","Martinez-Lopez N","Kao YR","Chen J","Stransky S","Steidl U","Moulik D","Ma Y","Sundaravel S","Sidoli S","Tatiparthy M","Reisz JA","Grimm J","Zintiridou A","Aivalioti MM","Sun D","Kumari R","Singh R","Will B","Ng A"],"additional_accession":[]},"is_claimable":false,"name":"An iron rheostat controls hematopoietic stem cell fate.","description":"Mechanisms governing the maintenance of blood-producing hematopoietic stem and multipotent progenitor cells (HSPCs) are incompletely understood, particularly those regulating fate, ensuring long-term maintenance, and preventing aging-associated stem cell dysfunction. We uncovered a role for transitory free cytoplasmic iron as a rheostat for adult stem cell fate control. We found that HSPCs harbor comparatively small amounts of free iron and show the activation of a conserved molecular response to limited iron-particularly during mitosis. To study the functional and molecular consequences of iron restriction, we developed models allowing for transient iron bioavailability limitation and combined single-molecule RNA quantification, metabolomics, and single-cell transcriptomic analyses with functional studies. Our data reveal that the activation of the limited iron response triggers coordinated metabolic and epigenetic events, establishing stemness-conferring gene regulation. Notably, we find that aging-associated cytoplasmic iron loading reversibly attenuates iron-dependent cell fate control, explicating intervention strategies for dysfunctional aged stem cells.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Mar","modification":"2026-06-01T22:06:41.476Z","creation":"2025-04-04T02:12:24.222Z"},"accession":"S-EPMC10939794","cross_references":{"pubmed":["38402617"],"doi":["10.1016/j.stem.2024.01.011"]}}