ArticleNature medicine2016
Rps14 haploinsufficiency causes a block in erythroid differentiation mediated by S100A8 and S100A9.
Article in Nature medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT03907553 (Aging of Hematopoietic Stem Cells - Molecular Architecture of Marrow Dysplasia and Clinical Contribution of Ineffective Hematopoiesis to Frailty in the Elderly), which is not on this map. Cited by 147 papers.
What it found
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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.
Aging of Hematopoietic Stem Cells - Molecular Architecture of Marrow Dysplasia and Clinical Contribution of Ineffective Hematopoiesis to Frailty in the Elderly
Who cites it
147 citing papers in PubMed, 245 citations in OpenAlex.
- Circulating S100A8 and S100A9 protein levels in plasma of patients with acquired aplastic anemia and myelodysplastic syndromes.Cytokine · 2019Trial
- Telomere shortening correlates with leukemic stem cell burden at diagnosis of chronic myeloid leukemia.Blood advances · 2018Trial
- Targeting TGFBR1 with the Investigational Inhibitor TP-6379 Improves Hematopoiesis in Low-Risk MDS Ex Vivo.Cells · 2026Article
- Hematopoietic mosaic chromosomal alterations are pleiotropic drivers of inflammaging, multimorbidity, and mortality.medRxiv : the preprint server for health sciences · 2026Article
- Inflammatory Signatures in MDS: The Missing Link Between Genetics, Microenvironment, and Therapy.Cells · 2026Review
- Article
- High serum ferritin is associated with genetic instability in myelodysplastic neoplasms.Journal of cancer research and clinical oncology · 2026Article
- Preclinical efficacy of tasquinimod in myelodysplastic neoplasms: Restoring erythropoiesis and mitigating bone loss.HemaSphere · 2026Article
- Mutant ribosomal protein RPS15 drives B cell malignancy through oxidative stress and genomic instability.Nature communications · 2026Article
- Aberrant Kupffer-like differentiation of hematopoietic stem cell is critical for the MDS pathogenesis in Setd2-deficient mice.Cell death and differentiation · 2026Article
- Ribosomal protein control of hematopoietic stem cell transformation through regulation of metabolism.Cell reports · 2025Article
- Clinical and Biological Insights into Myelodysplastic Neoplasms Associated with Deletions of Chromosome 5q Region.Hematology reports · 2025Review
- Innate immune mechanisms hijacked by leukemia-initiating stem cells for selective advantage and immune evasion in Ptpn11-associated JMML.Cell reports · 2025Article
- Non-essential role of S100A9 in hematopoiesis in primary MPN and MDS mouse models.Cancer biology & medicine · 2025Article
- Bone marrow microenvironment in myelodysplastic neoplasms: insights into pathogenesis, biomarkers, and therapeutic targets.Cancer cell international · 2025Review
- Fusobacterium nucleatum promotes colorectal cancer through neogenesis of tumor stem cells.The Journal of clinical investigation · 2025Article
- Genome sequencing in the management of myelodysplastic syndromes and related disorders.Haematologica · 2025Review
- Article
- Cross-organ protection of MSC-derived extracellular vesicles in ischemia-reperfusion injury: angiogenic synergy in kidney, brain, and heart.Frontiers in cardiovascular medicine · 2025Review
- Article
87 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
20 authors at 8 institutions in 2 countries.
Funding
Abstract
Impaired erythropoiesis in the deletion 5q (del(5q)) subtype of myelodysplastic syndrome (MDS) has been linked to heterozygous deletion of RPS14, which encodes the ribosomal protein small subunit 14. We generated mice with conditional inactivation of Rps14 and demonstrated an erythroid differentiation defect that is dependent on the tumor suppressor protein p53 (encoded by Trp53 in mice) and is characterized by apoptosis at the transition from polychromatic to orthochromatic erythroblasts. This defect resulted in age-dependent progressive anemia, megakaryocyte dysplasia and loss of hematopoietic stem cell (HSC) quiescence. As assessed by quantitative proteomics, mutant erythroblasts expressed higher levels of proteins involved in innate immune signaling, notably the heterodimeric S100 calcium-binding proteins S100a8 and S100a9. S100a8--whose expression was increased in mutant erythroblasts, monocytes and macrophages--is functionally involved in the erythroid defect caused by the Rps14 deletion, as addition of recombinant S100a8 was sufficient to induce a differentiation defect in wild-type erythroid cells, and genetic inactivation of S100a8 expression rescued the erythroid differentiation defect of Rps14-haploinsufficient HSCs. Our data link Rps14 haploinsufficiency in del(5q) MDS to activation of the innate immune system and induction of S100A8-S100A9 expression, leading to a p53-dependent erythroid differentiation defect.
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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.