ArticlePLoS biology2010
A key commitment step in erythropoiesis is synchronized with the cell cycle clock through mutual inhibition between PU.1 and S-phase progression.
Article in PLoS biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 129 papers.
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Who cites it
129 citing papers in PubMed, 180 citations in OpenAlex.
- The H3K4 methyltransferase KMT2D is an essential cofactor for GATA1 at erythroid gene enhancers.Nature communications · 2026Article
- Epo and hypoxia accelerate a pattern of gradual cell cycle shortening in BFU-e and CFU-e erythroid progenitors in vivo.Blood advances · 2026Article
- LDB1 represses fetal hemoglobin expression by enhancing BCL11A transcription.Redox biology · 2026Article
- Post-replicative chromatin accessibility predicts cell fate change.Stem cell reports · 2026Article
- p27Kip1 regulates γ-globin production.Blood · 2026Article
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- IL-17 stimulates erythropoiesis in vivo by amplifying the response of erythroid progenitors to erythropoietin.PLoS biology · 2025Article
- N6-methyladenosine regulation of mRNA translation is essential for early human erythropoiesis.bioRxiv : the preprint server for biology · 2025Article
- KLF1 coordinates specialized transcriptional networks required to maintain the integrity of terminal erythropoiesis.Journal of cell science · 2025Article
- Coupling and decoupling of the cell cycle from cell differentiation in development.Development (Cambridge, England) · 2025Review
- Trimodal Single-Cell Gene Regulatory Networks Reveal Principles of Stemness Loss and Cell Fate Acquisition in Human Hematopoiesis.bioRxiv : the preprint server for biology · 2025Article
- Impaired hematopoiesis and embryonic lethality at midgestation of mice lacking both lipid transfer proteins VPS13A and VPS13C.PLoS biology · 2025Article
- AK2-Deficient Mice Recapitulate Impaired Lymphopoiesis of Reticular Dysgenesis Patients, but Also Lack Erythropoiesis.European journal of immunology · 2025Article
- Ancient genomic linkage of α-globin and Nprl3 couples metabolism with erythropoiesis.Nature communications · 2025Article
- Cell state transitions are decoupled from cell division during early embryo development.Nature cell biology · 2024Article
- Chromatin structure and 3D architecture define the differential functions of PU.1 regulatory elements in blood cell lineages.Epigenetics & chromatin · 2024Article
- HES1 is required for mouse fetal hematopoiesis.Stem cell research & therapy · 2024Article
- Fetal liver macrophages contribute to the hematopoietic stem cell niche by controlling granulopoiesis.eLife · 2024Article
- Cell cycle-dependent activation of proneural transcription factor expression and reactive gliosis in rat Müller glia.Scientific reports · 2023Article
69 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
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Hematopoietic progenitors undergo differentiation while navigating several cell division cycles, but it is unknown whether these two processes are coupled. We addressed this question by studying erythropoiesis in mouse fetal liver in vivo. We found that the initial upregulation of cell surface CD71 identifies developmentally matched erythroblasts that are tightly synchronized in S-phase. We show that DNA replication within this but not subsequent cycles is required for a differentiation switch comprising rapid and simultaneous committal transitions whose precise timing was previously unknown. These include the onset of erythropoietin dependence, activation of the erythroid master transcriptional regulator GATA-1, and a switch to an active chromatin conformation at the β-globin locus. Specifically, S-phase progression is required for the formation of DNase I hypersensitive sites and for DNA demethylation at this locus. Mechanistically, we show that S-phase progression during this key committal step is dependent on downregulation of the cyclin-dependent kinase p57(KIP2) and in turn causes the downregulation of PU.1, an antagonist of GATA-1 function. These findings therefore highlight a novel role for a cyclin-dependent kinase inhibitor in differentiation, distinct to their known function in cell cycle exit. Furthermore, we show that a novel, mutual inhibition between PU.1 expression and S-phase progression provides a "synchromesh" mechanism that "locks" the erythroid differentiation program to the cell cycle clock, ensuring precise coordination of critical differentiation events.
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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.