{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T06:51:30Z","timestamp":1791615090248,"version":"4.3.4"},"reference-count":100,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,9,30]],"date-time":"2022-09-30T00:00:00Z","timestamp":1664496000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["ZIA BC 011924"],"award-info":[{"award-number":["ZIA BC 011924"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Hematopoiesis, a process that results in the differentiation of all blood lineages, is essential throughout life. The production of 1x10<jats:sup>12<\/jats:sup> blood cells per day, including 200x10<jats:sup>9<\/jats:sup> erythrocytes, is highly dependent on nutrient consumption. Notably though, the relative requirements for micronutrients during the perinatal period, a critical developmental window for immune cell and erythrocyte differentiation, have not been extensively studied. More specifically, the impact of the vitamin C\/ascorbate micronutrient on perinatal as compared to adult hematopoiesis has been difficult to assess in animal models. Even though humans cannot synthesize ascorbate, due to a pseudogenization of the L-gulono-\u03b3-lactone oxidase (<jats:italic>GULO<\/jats:italic>) gene, its generation from glucose is an ancestral mammalian trait. Taking advantage of a <jats:italic>Gulo<jats:sup>-\/-<\/jats:sup><\/jats:italic> mouse model, we show that ascorbic acid deficiency profoundly impacts perinatal hematopoiesis, resulting in a hypocellular bone marrow (BM) with a significant reduction in hematopoietic stem cells, multipotent progenitors, and hematopoietic progenitors. Furthermore, myeloid progenitors exhibited differential sensitivity to vitamin C levels; common myeloid progenitors and megakaryocyte-erythrocyte progenitors were markedly reduced in <jats:italic>Gulo<jats:sup>-\/-<\/jats:sup><\/jats:italic> pups following vitamin C depletion in the dams, whereas granulocyte-myeloid progenitors were spared, and their frequency was even augmented. Notably, hematopoietic cell subsets were rescued by vitamin C repletion. Consistent with these data, peripheral myeloid cells were maintained in ascorbate-deficient <jats:italic>Gulo<jats:sup>-\/-<\/jats:sup><\/jats:italic> pups while other lineage-committed hematopoietic cells were decreased. A reduction in B cell numbers was associated with a significantly reduced humoral immune response in ascorbate-depleted <jats:italic>Gulo<jats:sup>-\/-<\/jats:sup><\/jats:italic> pups but not adult mice. Erythropoiesis was particularly sensitive to vitamin C deprivation during both the perinatal and adult periods, with ascorbate-deficient <jats:italic>Gulo<jats:sup>-\/-<\/jats:sup><\/jats:italic> pups as well as adult mice exhibiting compensatory splenic differentiation. Furthermore, in the pathological context of hemolytic anemia, vitamin C-deficient adult <jats:italic>Gulo<jats:sup>-\/-<\/jats:sup><\/jats:italic> mice were not able to sufficiently increase their erythropoietic activity, resulting in a sustained anemia. Thus, vitamin C plays a pivotal role in the maintenance and differentiation of hematopoietic progenitors during the neonatal period and is required throughout life to sustain erythroid differentiation under stress conditions.<\/jats:p>","DOI":"10.3389\/fimmu.2022.898827","type":"journal-article","created":{"date-parts":[[2022,9,30]],"date-time":"2022-09-30T11:43:27Z","timestamp":1664538207000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Vitamin C deficiency reveals developmental differences between neonatal and adult 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