ArticleThe Journal of clinical investigation2015
Coordinate expression of heme and globin is essential for effective erythropoiesis.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 66 citations in OpenAlex.
- Pooled it
- The effect of tamoxifen on haematological parameters and iron status in laying hens.Poultry science · 2026Article
- Results from the first clinical trial of bitopertin for steroid-relapsed/refractory Diamond-Blackfan anemia.Blood red cells & iron · 2026Article
- ReducedInternational journal of molecular sciences · 2026Article
- LDB1 represses fetal hemoglobin expression by enhancing BCL11A transcription.Redox biology · 2026Article
- Beyond Hematologic Malignancies: Colorectal Cancer as a Solid Tumor Manifestation of Inherited Bone Marrow Failure Syndromes.International journal of molecular sciences · 2025Review
- Restricting glycine uptake with bitopertin improves erythropoiesis in preclinical models of Diamond-Blackfan anemia.Blood red cells & iron · 2025Article
- Outline of Iron Metabolism, with Emphasis on Erythroid Cells.Mediterranean journal of hematology and infectious diseases · 2025Review
- Analyzing the role of ferroptosis in ribosome-related bone marrow failure disorders: From pathophysiology to potential pharmacological exploitation.IUBMB life · 2024Review
- Article
- Unearthing FLVCR1a: tracing the path to a vital cellular transporter.Cellular and molecular life sciences : CMLS · 2024Review
- Mfsd7b facilitates choline transport and missense mutations affect choline transport function.Cellular and molecular life sciences : CMLS · 2023Article
- Vitamin C derivative/AA2P promotes erythroid differentiation by upregulatingLife medicine · 2023Article
- The transcriptomic landscape of normal and ineffective erythropoiesis at single-cell resolution.Blood advances · 2023Article
- Notes from the Underground: Heme Homeostasis inBiomolecules · 2023Review
- Animal models of Diamond-Blackfan anemia: updates and challenges.Haematologica · 2023Review
- Heme as a differentiation-regulatory transcriptional cofactor.International journal of hematology · 2022Review
- Article
- Fine-Tuning of Cholesterol Homeostasis Controls Erythroid Differentiation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Targeting elevated heme levels to treat a mouse model for Diamond-Blackfan Anemia.Experimental hematology · 2022Article
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
Erythropoiesis requires rapid and extensive hemoglobin production. Heme activates globin transcription and translation; therefore, heme synthesis must precede globin synthesis. As free heme is a potent inducer of oxidative damage, its levels within cellular compartments require stringent regulation. Mice lacking the heme exporter FLVCR1 have a severe macrocytic anemia; however, the mechanisms that underlie erythropoiesis dysfunction in these animals are unclear. Here, we determined that erythropoiesis failure occurs in these animals at the CFU-E/proerythroblast stage, a point at which the transferrin receptor (CD71) is upregulated, iron is imported, and heme is synthesized--before ample globin is produced. From the CFU-E/proerythroblast (CD71(+) Ter119(-) cells) stage onward, erythroid progenitors exhibited excess heme content, increased cytoplasmic ROS, and increased apoptosis. Reducing heme synthesis in FLVCR1-defient animals via genetic and biochemical approaches improved the anemia, implying that heme excess causes, and is not just associated with, the erythroid marrow failure. Expression of the cell surface FLVCR1 isoform, but not the mitochondrial FLVCR1 isoform, restored normal rbc production, demonstrating that cellular heme export is essential. Together, these studies provide insight into how heme is regulated to allow effective erythropoiesis, show that erythropoiesis fails when heme is excessive, and emphasize the importance of evaluating Ter119(-) erythroid cells when studying erythroid marrow failure in murine models.
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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.