ArticleBlood advances2023
A critical role of RUNX1 in governing megakaryocyte-primed hematopoietic stem cell differentiation.
Article in Blood advances, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 27 citations in OpenAlex.
- Megakaryocytes in myelofibrosis: mechanisms of fibrotic niche remodeling and therapeutic implications.Biomarker research · 2026Review
- Tet2 deficiency drives age-related heterogeneous progression of myeloid neoplasms through epigenetic-immune microenvironment imbalance.Journal of translational medicine · 2026Article
- Geneformer-guided multiomics integration identifies Pbx1 as a network hub of hematopoietic stem cell aging.Science advances · 2026Article
- Glycosylation orchestrates megakaryocytic fate of hematopoietic stem cells via Wnt-MUC13 signaling.Nature communications · 2026Article
- Epigenetic programming by H3K23ac defines lineage fate of Meg3Nature cell biology · 2026Article
- Shifting IRES versus Cap-initiated translation during homeostatic stem cell differentiation and stress.Science advances · 2026Article
- The mitochondria-targeting compound PTC299 enhances megakaryocyte and platelet production.Stem cells translational medicine · 2026Article
- Interleukin-12 Supports Self-renewal Division of Mouse Hematopoietic Stem Cells in Polyvinyl Alcohol-Based Culture.Stem cell reviews and reports · 2026Article
- Danthron as a novel IL-6R agonist promotes thrombopoiesis via the SRC/RAS/MAPK pathway.Frontiers in immunology · 2026Article
- Molecular alterations in the GATA-2, RUNX1, C/EBPα and hTERT genes in patients with aplastic anemia by MLPA.Genetics and molecular biology · 2026Article
- The Dual Role of RUNX1 in Inflammation-Driven Age-Related Diseases: From Molecular Mechanisms to Clinical Translation.Biomedicines · 2025Review
- Differentiation stage-specific use of cap-independent and cap-dependent translation initiation in hematopoiesis.bioRxiv : the preprint server for biology · 2025Article
- RUNX1A isoform is overexpressed in acute myeloid leukemia and is associated with FLT3 internal tandem duplications.Cancer gene therapy · 2025Article
- New insights into the generation and function of megakaryocytes in health and disease.Haematologica · 2025Review
- Defining 2 biologically and clinically distinct groups in acute leukemia with a mixed phenotype.Blood · 2025Article
- A germlineScience advances · 2025Article
- Myelodysplastic syndrome with dual germline RUNX1 and DDX41 variants: a rare genetic predisposition case.Familial cancer · 2025Article
- Inherited Predispositions to Myeloid Neoplasms: Pathogenesis and Clinical Implications.Annual review of pathology · 2025Review
- CXCR4 signaling determines the fate of hematopoietic multipotent progenitors by stimulating mTOR activity and mitochondrial metabolism.Science signaling · 2024Article
- Modeling blood-brain barrier formation and cerebral cavernous malformations in human PSC-derived organoids.Cell stem cell · 2024Article
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
As a transcription factor in the RUNT domain core-binding factor family, RUNX1 is crucial in multiple stages of hematopoiesis, and its mutation can cause familial platelet disorder with a predisposition to acute myeloid leukemia. Previous work has established that RUNX1 is involved in the maturation of megakaryocytes (MKs) and the production of platelets. Recent studies have shown that there exists a subpopulation of hematopoietic stem cells (HSCs) with relatively high expression of von Willebrand factor and CD41 at the apex of the HSC hierarchy, termed MK-HSCs, which can give rise to MKs without going through the traditional differentiation trajectory from HSC via MPP (multipotent progenitors) and MEP (megakaryocyte-erythroid progenitor). Here, by using Runx1F/FMx1-Cre mouse model, we discovered that the MK-HSC to MK direct differentiation can occur within 1 cell division, and RUNX1 is an important regulator in the process. Runx1 knockout results in a drastic decrease in platelet counts and a severe defect in the differentiation from MK-HSCs to MKs. Single cell RNA sequencing (RNAseq) analysis shows that MK-HSCs have a distinct gene expression signature compared with non-MK-HSCs, and Runx1 deletion alters the platelet and MK-related gene expression in MK-HSCs. Furthermore, bulk RNAseq and Cut&Run analyses show that RUNX1 binds to multiple essential MK or platelet developmental genes, such as Spi1, Selp, and Itga2b and regulates their expressions in MK-HSCs. Thus, by modulating the expression of MK-related genes, RUNX1 governs the direct differentiation from MK-HSCs to MKs and platelets.
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