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In this study, we show that deletion of the Slc23a2 ascorbate transporter from hematopoietic cells depleted ascorbate to undetectable levels in HSCs and multipotent hematopoietic progenitors (MPPs) without altering the plasma ascorbate levels. Slc23a2 deficiency increased HSC reconstituting potential and self-renewal potential upon transplantation into irradiated mice. Slc23a2 deficiency also increased the reconstituting and self-renewal potentials of MPPs, conferring the ability to reconstitute irradiated mice long term. Slc23a2-deficient HSCs and MPPs divided much less frequently than control HSCs and MPPs. Increased self-renewal and reconstituting potential were observed particularly in quiescent Slc23a2-deficient HSCs and MPPs. The effect of Slc23a2 deficiency on MPP self-renewal was not mediated by reduced Tet2 function. Ascorbate thus regulates quiescence and restricts self-renewal potential in HSCs and MPPs such that ascorbate deficiency confers MPPs with long-term self-renewal potential.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1182\/blood.2024024769","type":"journal-article","created":{"date-parts":[[2024,10,22]],"date-time":"2024-10-22T18:00:39Z","timestamp":1729620039000},"page":"114-126","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":16,"title":["Ascorbate deficiency increases quiescence and self-renewal in hematopoietic stem cells and multipotent progenitors"],"prefix":"10.1182","volume":"145","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9912-5177","authenticated-orcid":false,"given":"Stefano","family":"Comazzetto","sequence":"first","affiliation":[{"name":"1Department of Pediatrics, Children\u2019s Research Institute, University of Texas Southwestern Medical Center, Dallas, 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