Vitamin C deficiency reveals developmental differences between neonatal and adult hematopoiesis.

Autor:	Phadke I; Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD, United States.; Institut de Génétique Moléculaire de Montpellier, University of Montpellier, Centre National de la Recherche Scientifique (CNRS), Montpellier, France.; Laboratory of Excellence GR-Ex, Paris, France., Pouzolles M; Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD, United States., Machado A; Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD, United States.; Institut de Génétique Moléculaire de Montpellier, University of Montpellier, Centre National de la Recherche Scientifique (CNRS), Montpellier, France.; Laboratory of Excellence GR-Ex, Paris, France., Moraly J; Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD, United States., Gonzalez-Menendez P; Institut de Génétique Moléculaire de Montpellier, University of Montpellier, Centre National de la Recherche Scientifique (CNRS), Montpellier, France.; Laboratory of Excellence GR-Ex, Paris, France., Zimmermann VS; Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD, United States.; Institut de Génétique Moléculaire de Montpellier, University of Montpellier, Centre National de la Recherche Scientifique (CNRS), Montpellier, France.; Laboratory of Excellence GR-Ex, Paris, France., Kinet S; Institut de Génétique Moléculaire de Montpellier, University of Montpellier, Centre National de la Recherche Scientifique (CNRS), Montpellier, France.; Laboratory of Excellence GR-Ex, Paris, France., Levine M; Molecular and Clinical Nutrition Section, Intramural Research Program, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, United States., Violet PC; Molecular and Clinical Nutrition Section, Intramural Research Program, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, United States., Taylor N; Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD, United States.; Institut de Génétique Moléculaire de Montpellier, University of Montpellier, Centre National de la Recherche Scientifique (CNRS), Montpellier, France.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2022 Sep 30; Vol. 13, pp. 898827. Date of Electronic Publication: 2022 Sep 30 (Print Publication: 2022).
DOI:	10.3389/fimmu.2022.898827
Abstrakt:	Hematopoiesis, a process that results in the differentiation of all blood lineages, is essential throughout life. The production of 1x10 12 blood cells per day, including 200x10 9 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-γ-lactone oxidase ( GULO ) gene, its generation from glucose is an ancestral mammalian trait. Taking advantage of a Gulo -/- 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 Gulo -/- 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 Gulo -/- 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 Gulo -/- pups but not adult mice. Erythropoiesis was particularly sensitive to vitamin C deprivation during both the perinatal and adult periods, with ascorbate-deficient Gulo -/- pups as well as adult mice exhibiting compensatory splenic differentiation. Furthermore, in the pathological context of hemolytic anemia, vitamin C-deficient adult Gulo -/- 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. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Phadke, Pouzolles, Machado, Moraly, Gonzalez-Menendez, Zimmermann, Kinet, Levine, Violet and Taylor.)
Databáze:	MEDLINE
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