ArticlePLoS genetics2016
RUNX1B Expression Is Highly Heterogeneous and Distinguishes Megakaryocytic and Erythroid Lineage Fate in Adult Mouse Hematopoiesis.
Article in PLoS genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 36 citations in OpenAlex.
- Single-cell profiling reveals three endothelial-to-hematopoietic transitions with divergent isoform expression landscapes.Nature cardiovascular research · 2025Article
- Emerging Roles of Megakaryocytes in Immune Regulation and Potential Therapeutic Prospects.Cells · 2025Review
- RUNX1 isoforms regulate RUNX1 and target genes differentially in platelets-megakaryocytes: association with clinical cardiovascular events.Journal of thrombosis and haemostasis : JTH · 2024Article
- Interface-guided phenotyping of coding variants in the transcription factor RUNX1.Cell reports · 2024Article
- RUNX1 Isoforms Regulate RUNX1 and Target-Genes Differentially in Platelets-Megakaryocytes: Association with Clinical Cardiovascular Events.bioRxiv : the preprint server for biology · 2024Article
- Age-related promoter-switch regulates Runx1 expression in adult rat hearts.BMC cardiovascular disorders · 2023Article
- Slc35a1 deficiency causes thrombocytopenia due to impaired megakaryocytopoiesis and excessive platelet clearance in the liver.Haematologica · 2021Article
- Long Non-coding RNAs and MicroRNAs Interplay in Osteogenic Differentiation of Mesenchymal Stem Cells.Frontiers in cell and developmental biology · 2021Review
- RUNX1-205, a novel splice variant of the human RUNX1 gene, has blockage effect on mesoderm-hemogenesis transition and promotion effect during the late stage of hematopoiesis.Journal of molecular cell biology · 2020Article
- RUNX1 Dosage in Development and Cancer.Molecules and cells · 2020Review
- Transcriptional control of blood cell emergence.FEBS letters · 2019Review
- RUNX1-ETO: Attacking the Epigenome for Genomic Instable Leukemia.International journal of molecular sciences · 2019Review
- Interplay between transcription regulators RUNX1 and FUBP1 activates an enhancer of the oncogene c-KIT and amplifies cell proliferation.Nucleic acids research · 2018Article
- The Oncogenic Transcription Factor RUNX1/ETO Corrupts Cell Cycle Regulation to Drive Leukemic Transformation.Cancer cell · 2018Article
- Poly(C)-Binding Protein Pcbp2 Enables Differentiation of Definitive Erythropoiesis by Directing Functional Splicing of the Runx1 Transcript.Molecular and cellular biology · 2018Article
- Regulation of RUNX1 dosage is crucial for efficient blood formation from hemogenic endothelium.Development (Cambridge, England) · 2018Article
- Protein arginine methyltransferase 6 controls erythroid gene expression and differentiation of human CD34Haematologica · 2018Article
- A novel prospective isolation of murine fetal liver progenitors to study in utero hematopoietic defects.PLoS genetics · 2018Article
- Transcription Factor RUNX1 Regulates PlateletCirculation · 2017Article
- Article
Corrections and comments
- Erratum issued
Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
The Core Binding Factor (CBF) protein RUNX1 is a master regulator of definitive hematopoiesis, crucial for hematopoietic stem cell (HSC) emergence during ontogeny. RUNX1 also plays vital roles in adult mice, in regulating the correct specification of numerous blood lineages. Akin to the other mammalian Runx genes, Runx1 has two promoters P1 (distal) and P2 (proximal) which generate distinct protein isoforms. The activities and specific relevance of these two promoters in adult hematopoiesis remain to be fully elucidated. Utilizing a dual reporter mouse model we demonstrate that the distal P1 promoter is broadly active in adult hematopoietic stem and progenitor cell (HSPC) populations. By contrast the activity of the proximal P2 promoter is more restricted and its upregulation, in both the immature Lineage- Sca1high cKithigh (LSK) and bipotential Pre-Megakaryocytic/Erythroid Progenitor (PreMegE) populations, coincides with a loss of erythroid (Ery) specification. Accordingly the PreMegE population can be prospectively separated into "pro-erythroid" and "pro-megakaryocyte" populations based on Runx1 P2 activity. Comparative gene expression analyses between Runx1 P2+ and P2- populations indicated that levels of CD34 expression could substitute for P2 activity to distinguish these two cell populations in wild type (WT) bone marrow (BM). Prospective isolation of these two populations will enable the further investigation of molecular mechanisms involved in megakaryocytic/erythroid (Mk/Ery) cell fate decisions. Having characterized the extensive activity of P1, we utilized a P1-GFP homozygous mouse model to analyze the impact of the complete absence of Runx1 P1 expression in adult mice and observed strong defects in the T cell lineage. Finally, we investigated how the leukemic fusion protein AML1-ETO9a might influence Runx1 promoter usage. Short-term AML1-ETO9a induction in BM resulted in preferential P2 upregulation, suggesting its expression may be important to establish a pre-leukemic environment.
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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.