ArticleNature medicine2014
Megakaryocytes regulate hematopoietic stem cell quiescence through CXCL4 secretion.
Article in Nature medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 374 papers.
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Who cites it
374 citing papers in PubMed, 586 citations in OpenAlex.
- Combination of dociparstat sodium (DSTAT), a CXCL12/CXCR4 inhibitor, with azacitidine for the treatment of hypomethylating agent refractory AML and MDS.Leukemia research · 2021Trial
- Megakaryocytes in myelofibrosis: mechanisms of fibrotic niche remodeling and therapeutic implications.Biomarker research · 2026Review
- A cryptic symmetry switch allosterically controls how the PF4 self-protein turns into a pathogenic antigen.Nature communications · 2026Article
- Inhibition of RhoA-mediated secretory autophagy in megakaryocytes mitigates myelofibrosis in mice.Nature communications · 2026Article
- Radiosensitive HSPC Subsets Define Early Hematopoietic Injury and Enable H-ARS Therapeutic Screening.Current issues in molecular biology · 2026Article
- Ki-67 Expression in megakaryocytes: A new prognostic marker in Myelodysplastic Syndromes.Virchows Archiv : an international journal of pathology · 2026Article
- Nascent preplatelets and B4GALT1 glycosylation contribute to 5-FU-induced bone marrow recovery.Blood advances · 2026Article
- The Role of the Bone Marrow Microenvironment in the Pathogenesis of Acute Myeloid Leukemia.Biomedicines · 2026Review
- Review
- Megakaryocytes: An Immune Complex Cell Type.Circulation research · 2026Article
- Endosteal integrin-α8⁺ mesenchymal stem cells maintain haematopoietic stem cell function via extracellular matrix-mediated interactions.Nature communications · 2026Article
- Immunomodulatory role of megakaryocytes in the hematopoietic niche of myeloproliferative neoplasms.Haematologica · 2026Article
- Bone Marrow Failure Model Mimics Aplastic Anemia Patients: Single-Cell Landscape of Immune Response Reveals Novel Mechanisms of Immune Imbalance in AA.Cancer medicine · 2026Article
- Aging mechanisms and rejuvenation strategies for hematopoietic stem cells.Genome biology · 2026Review
- Hematopoietic stem and progenitor cell hierarchy is established by thrombopoietin-driven neonatal hematopoiesis.Stem cell reports · 2026Article
- Overexpression of the TGF-β target CCN2 in megakaryocytes: a common feature of MDS with mutated SF3B1 : Uncovering novelinsights into the bone marrow microenvironment in MDS.Virchows Archiv : an international journal of pathology · 2026Article
- Metabolic and epigenetic interplay in HSPC specification: A balance between extrinsic and intrinsic cues.iScience · 2026Review
- Hematopoietic Niche Hijacking in Bone Metastases: Roles of Megakaryocytes, Erythroid Lineage Cells, and Perivascular Stromal Subsets.Biomedicines · 2026Review
- Platelet factor 4 in cognitive, immune and hematopoietic aging: emerging evidence and translational challenges.Frontiers in immunology · 2026Review
- Pediatric leukemia: origins, pathogenesis, the role of microenvironment and immunological modulation.Frontiers in immunology · 2026Review
314 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
In the bone marrow, hematopoietic stem cells (HSCs) lodge in specialized microenvironments that tightly control the proliferative state of HSCs to adapt to the varying needs for replenishment of blood cells while also preventing HSC exhaustion. All putative niche cells suggested thus far have a nonhematopoietic origin. Thus, it remains unclear how feedback from mature cells is conveyed to HSCs to adjust their proliferation. Here we show that megakaryocytes (MKs) can directly regulate HSC pool size in mice. Three-dimensional whole-mount imaging revealed that endogenous HSCs are frequently located adjacent to MKs in a nonrandom fashion. Selective in vivo depletion of MKs resulted in specific loss of HSC quiescence and led to a marked expansion of functional HSCs. Gene expression analyses revealed that MKs are the source of chemokine C-X-C motif ligand 4 (CXCL4, also named platelet factor 4 or PF4) in the bone marrow, and we found that CXCL4 regulates HSC cell cycle activity. CXCL4 injection into mice resulted in a reduced number of HSCs because of their increased quiescence. By contrast, Cxcl4(-/-) mice exhibited an increased number of HSCs and increased HSC proliferation. Combined use of whole-mount imaging and computational modeling was highly suggestive of a megakaryocytic niche capable of independently influencing HSC maintenance by regulating quiescence. These results indicate that a terminally differentiated cell type derived from HSCs contributes to the HSC niche, directly regulating HSC behavior.
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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.