ArticleScientific reports2016
CXCR4/CXCL12 axis counteracts hematopoietic stem cell exhaustion through selective protection against oxidative stress.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 92 citations in OpenAlex.
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- Intrinsic and niche-dependent metabolic regulation of haematopoietic stem cells and implications for leukaemogenesis.Nature cell biology · 2026Review
- Bnip3lb-driven mitophagy maintains fate of the embryonic hematopoietic stem cell pool.Nature communications · 2026Article
- CXCR4 induces memory formation over exhaustion in CAR-T cells to achieve durable leukemia targeting.Nature communications · 2026Article
- Pediatric leukemia: origins, pathogenesis, the role of microenvironment and immunological modulation.Frontiers in immunology · 2026Review
- Metabolomics of healthy hematopoietic stem cells and leukemic stem cells.Journal of clinical and translational research · 2025Article
- Hematological Consequences of Environmental Change During Dewilding of Rhesus Macaques.Research square · 2025Article
- Leukemic Cells Hijack Stromal Bioelectricity to Reprogram the Bone Marrow Niche via CaV1.2-Dependent Mechanisms.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Clec12a is required for the pathogenesis of NUP98::NSD1 AML.Blood advances · 2025Article
- Untangling Ariadne's Thread Within the Bone Marrow Maze: A Close-Up View of Stem/Progenitor Cells' Interactome and Secretome.Advances in experimental medicine and biology · 2025Review
- CHIP: a clonal odyssey of the bone marrow niche.The Journal of clinical investigation · 2024Review
- A simultaneous knockout knockin genome editing strategy in HSPCs potently inhibits CCR5- and CXCR4-tropic HIV-1 infection.Cell stem cell · 2024Article
- Deciphering the evolving niche interactome of human hematopoietic stem cells from ontogeny to aging.Frontiers in molecular biosciences · 2024Article
- The evolving hematopoietic niche during development.Frontiers in molecular biosciences · 2024Review
- Inflammation and aging: signaling pathways and intervention therapies.Signal transduction and targeted therapy · 2023Review
- The Triterpenoid Nrf2 Activator, CDDO-Me, Decreases Neutrophil Senescence in a Murine Model of Joint Damage.International journal of molecular sciences · 2023Article
- The Bone Marrow Immune Microenvironment in CML: Treatment Responses, Treatment-Free Remission, and Therapeutic Vulnerabilities.Current hematologic malignancy reports · 2023Review
- An "unexpected" role for EMT transcription factors in hematological development and malignancy.Frontiers in immunology · 2023Review
Corrections and comments
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Authors and funding
17 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hematopoietic stem cells (HSCs) undergo self-renewal to maintain hematopoietic homeostasis for lifetime, which is regulated by the bone marrow (BM) microenvironment. The chemokine receptor CXCR4 and its ligand CXCL12 are critical factors supporting quiescence and BM retention of HSCs. Here, we report an unknown function of CXCR4/CXCL12 axis in the protection of HSCs against oxidative stress. Disruption of CXCR4 receptor in mice leads to increased endogenous production of reactive oxygen species (ROS), resulting in p38 MAPK activation, increased DNA double-strand breaks and apoptosis leading to marked reduction in HSC repopulating potential. Increased ROS levels are directly responsible for exhaustion of the HSC pool and are not linked to loss of quiescence of CXCR4-deficient HSCs. Furthermore, we report that CXCL12 has a direct rescue effect on oxidative stress-induced HSC damage at the mitochondrial level. These data highlight the importance of CXCR4/CXCL12 axis in the regulation of lifespan of HSCs by limiting ROS generation and genotoxic stress.
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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.