ArticleCell reports2021
An IDH1-vitamin C crosstalk drives human erythroid development by inhibiting pro-oxidant mitochondrial metabolism.
Article in Cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 57 citations in OpenAlex.
- ZEB1 drives terminal erythroid maturation by controlling the GATA2-KLF1 regulatory switch.Nucleic acids research · 2026Article
- Oxidative Stress and Mitochondrial Dysfunction in Myelodysplastic Syndrome: Roles in Development, Diagnosis, Prognosis, and Treatment.International journal of molecular sciences · 2025Review
- The involvement of mitochondria in erythrocyte pathology and diseases: from mechanisms to therapeutic strategies.Clinical and experimental medicine · 2025Review
- Article
- Youthful Stem Cell Microenvironments: Rejuvenating Aged Bone Repair Through Mitochondrial Homeostasis Remodeling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Article
- Nucleotide depletion promotes cell fate transitions by inducing DNA replication stress.Developmental cell · 2024Article
- Mitochondrial regulation of erythropoiesis in homeostasis and disease.British journal of haematology · 2024Review
- Dietary cysteine and methionine promote peroxisome elevation and fat loss by induction of CG33474 expression in Drosophila adipose tissue.Cellular and molecular life sciences : CMLS · 2024Article
- Ascorbate depletion increases quiescence and self-renewal potential in hematopoietic stem cells and multipotent progenitors.bioRxiv : the preprint server for biology · 2024Article
- The interactions between ineffective erythropoiesis and ferroptosis in β-thalassemia.Frontiers in physiology · 2024Review
- Unraveling the 2,3-diketo-L-gulonic acid-dependent and -independent impacts of L-ascorbic acid on somatic cell reprogramming.Cell & bioscience · 2023Article
- Nutrient regulation of development and cell fate decisions.Development (Cambridge, England) · 2023Review
- Vitamin C derivative/AA2P promotes erythroid differentiation by upregulatingLife medicine · 2023Article
- Arginine metabolism regulates human erythroid differentiation through hypusination of eIF5A.Blood · 2023Article
- Natural Morin-Based Metal Organic Framework Nanoenzymes Modulate Articular Cavity Microenvironment to Alleviate Osteoarthritis.Research (Washington, D.C.) · 2023Article
- Expansion and differentiation of ex vivo cultured erythroblasts in scalable stirred bioreactors.Biotechnology and bioengineering · 2022Article
- The accumulation of miR-125b-5p is indispensable for efficient erythroblast enucleation.Cell death & disease · 2022Article
- Construction of a transposase accessible chromatin landscape reveals chromatin state of repeat elements and potential causal variant for complex traits in pigs.Journal of animal science and biotechnology · 2022Article
- Centrosome function is critical during terminal erythroid differentiation.The EMBO journal · 2022Article
Corrections and comments
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Authors and funding
23 authors at 10 institutions in 3 countries.
Funding
Abstract
The metabolic changes controlling the stepwise differentiation of hematopoietic stem and progenitor cells (HSPCs) to mature erythrocytes are poorly understood. Here, we show that HSPC development to an erythroid-committed proerythroblast results in augmented glutaminolysis, generating alpha-ketoglutarate (αKG) and driving mitochondrial oxidative phosphorylation (OXPHOS). However, sequential late-stage erythropoiesis is dependent on decreasing αKG-driven OXPHOS, and we find that isocitrate dehydrogenase 1 (IDH1) plays a central role in this process. IDH1 downregulation augments mitochondrial oxidation of αKG and inhibits reticulocyte generation. Furthermore, IDH1 knockdown results in the generation of multinucleated erythroblasts, a morphological abnormality characteristic of myelodysplastic syndrome and congenital dyserythropoietic anemia. We identify vitamin C homeostasis as a critical regulator of ineffective erythropoiesis; oxidized ascorbate increases mitochondrial superoxide and significantly exacerbates the abnormal erythroblast phenotype of IDH1-downregulated progenitors, whereas vitamin C, scavenging reactive oxygen species (ROS) and reprogramming mitochondrial metabolism, rescues erythropoiesis. Thus, an IDH1-vitamin C crosstalk controls terminal steps of human erythroid differentiation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.