ArticleBlood2016
EKLF/KLF1-regulated cell cycle exit is essential for erythroblast enucleation.
Article in Blood, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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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.
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Who cites it
65 citing papers in PubMed, 86 citations in OpenAlex.
- EpoR stimulates rapid cycling and larger red cells during mouse and human erythropoiesis.Nature communications · 2021Trial
- ZEB1 drives terminal erythroid maturation by controlling the GATA2-KLF1 regulatory switch.Nucleic acids research · 2026Article
- ReducedInternational journal of molecular sciences · 2026Article
- Orai1 acts as a novel CaExperimental & molecular medicine · 2026Article
- p27Kip1 regulates γ-globin production.Blood · 2026Article
- Article
- Global comprehensive transcriptomic and proteomic analyses of murine terminal erythroid differentiation.Global medical genetics · 2025Article
- Mitochondrial iron transport via MFRN1 is required for erythroid cell cycle progression.Blood advances · 2025Article
- KLF1 coordinates specialized transcriptional networks required to maintain the integrity of terminal erythropoiesis.Journal of cell science · 2025Article
- The oncogene protein kinase PIM1 regulates mammalian erythroblast enucleation.Communications biology · 2025Article
- Disrupting ZBTB7A or BCL11A binding sites reactivates fetal hemoglobin in erythroblasts from healthy and βScientific reports · 2025Article
- Causal modeling of gene effects from regulators to programs to traits: integration of genetic associations and Perturb-seq.bioRxiv : the preprint server for biology · 2025Article
- Serine Hydroxymethyltransferase 2 Deficiency in the Hematopoietic System Disrupts Erythropoiesis and Induces Anemia in Murine Models.International journal of molecular sciences · 2024Article
- Erythroblast enucleation at a glance.Journal of cell science · 2024Review
- Mutations in linker-2 of KLF1 impair expression of membrane transporters and cytoskeletal proteins causing hemolysis.Nature communications · 2024Article
- Entire expressed peripheral blood transcriptome in pediatric severe malarial anemia.Nature communications · 2024Article
- Erythroid Krüppel-Like Factor (KLF1): A Surprisingly Versatile Regulator of Erythroid Differentiation.Advances in experimental medicine and biology · 2024Review
- Multidimensional profiling reveals GATA1-modulated stage-specific chromatin states and functional associations during human erythropoiesis.Nucleic acids research · 2023Article
- Review
- Identification of a genomic DNA sequence that quantitatively modulates KLF1 transcription factor expression in differentiating human hematopoietic cells.Scientific reports · 2023Article
5 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The mechanisms regulating the sequential steps of terminal erythroid differentiation remain largely undefined, yet are relevant to human anemias that are characterized by ineffective red cell production. Erythroid Krüppel-like Factor (EKLF/KLF1) is a master transcriptional regulator of erythropoiesis that is mutated in a subset of these anemias. Although EKLF's function during early erythropoiesis is well studied, its role during terminal differentiation has been difficult to functionally investigate due to the impaired expression of relevant cell surface markers in Eklf(-/-) erythroid cells. We have circumvented this problem by an innovative use of imaging flow cytometry to investigate the role of EKLF in vivo and have performed functional studies using an ex vivo culture system that enriches for terminally differentiating cells. We precisely define a previously undescribed block during late terminal differentiation at the orthochromatic erythroblast stage for Eklf(-/-) cells that proceed beyond the initial stall at the progenitor stage. These cells efficiently decrease cell size, condense their nucleus, and undergo nuclear polarization; however, they display a near absence of enucleation. These late-stage Eklf(-/-) cells continue to cycle due to low-level expression of p18 and p27, a new direct target of EKLF. Surprisingly, both cell cycle and enucleation deficits are rescued by epistatic reintroduction of either of these 2 EKLF target cell cycle inhibitors. We conclude that the cell cycle as regulated by EKLF during late stages of differentiation is inherently critical for enucleation of erythroid precursors, thereby demonstrating a direct functional relationship between cell cycle exit and nuclear expulsion.
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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.