ArticleStem cells (Dayton, Ohio)2012
CXCL12 enhances human neural progenitor cell survival through a CXCR7- and CXCR4-mediated endocytotic signaling pathway.
Article in Stem cells (Dayton, Ohio), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 84 citations in OpenAlex.
- The common variants implicated in microstructural abnormality of first episode and drug-naïve patients with schizophrenia.Scientific reports · 2017Trial
- Pharmacological modulation of CXCL12/CXCR4/ACKR3 for brain disorders - an overview.Cell communication and signaling : CCS · 2026Review
- Age-dependent effects of chronic traumatic and social isolation stress on mice social behavior.Neurobiology of stress · 2026Article
- Thyroid hormone promotes fetal neurogenesis.JCI insight · 2025Article
- Mesenchymal Stem Cells-Involved Strategies for Rheumatoid Arthritis Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Review
- CXCL12/CXCR4/CXCR7 axis in placenta tissues of patients with placenta previa.Open life sciences · 2023Article
- Neuritin Promotes Bone Marrow-Derived Mesenchymal Stem Cell Migration to Treat Diabetic Peripheral Neuropathy.Molecular neurobiology · 2022Article
- Comparison of the Response to the CXCR4 Antagonist AMD3100 during the Development of Retinal Organoids Derived from ES Cells and Zebrafish Retina.International journal of molecular sciences · 2022Article
- Ackr3-Venus knock-in mouse lights up brain vasculature.Molecular brain · 2021Article
- Pro- and Antiangiogenic Factors in Gliomas: Implications for Novel Therapeutic Possibilities.International journal of molecular sciences · 2021Review
- Gain of CXCR7 function with mesenchymal stem cell therapy ameliorates experimental arthritis via enhancing tissue regeneration and immunomodulation.Stem cell research & therapy · 2021Article
- The Role of Selected Chemokines and Their Receptors in the Development of Gliomas.International journal of molecular sciences · 2020Review
- RAMP3 determines rapid recycling of atypical chemokine receptor-3 for guided angiogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Small molecule ONC201 inhibits HIV-1 replication in macrophages via FOXO3a and TRAIL.Antiviral research · 2019Article
- Emerging roles of atypical chemokine receptor 3 (ACKR3) in normal development and physiology.Cytokine · 2018Review
- A guide to chemokines and their receptors.The FEBS journal · 2018Review
- Enzalutamide and CXCR7 inhibitor combination treatment suppresses cell growth and angiogenic signaling in castration-resistant prostate cancer models.International journal of cancer · 2018Article
- Zika virus propagation and release in human fetal astrocytes can be suppressed by neutral sphingomyelinase-2 inhibitor GW4869.Cell discovery · 2018Article
- Transplantation of iPS cell-derived neural progenitors overexpressing SDF-1α increases regeneration and functional recovery after ischemic stroke.Oncotarget · 2017Article
- Glutaminase C overexpression in the brain induces learning deficits, synaptic dysfunctions, and neuroinflammation in mice.Brain, behavior, and immunity · 2017Article
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 2 countries.
Funding
Abstract
Chemokine CXCL12 is widely expressed in the central nervous system and essential for the proper functioning of human neural progenitor cells (hNPCs). Although CXCL12 is known to function through its receptor CXCR4, recent data have suggested that CXCL12 binds to chemokine receptor CXCR7 with higher affinity than to CXCR4. However, little is known about the function of CXCR7 in hNPCs. Using a primary hNPC culture system, we demonstrated that CXCL12 promotes hNPC survival in the events of camptothecin-induced apoptosis or growth factor deprivation, and that this effect requires both CXCR7 and CXCR4. Through fluorescence-activated cell sorting analysis and immunocytochemistry, we determined that CXCR7 is mainly localized in the early endosome, while CXCR4 is more broadly expressed at the cell surface and on both early and recycling endosomes. Furthermore, we found that endocytosis is required for the prosurvival function of CXCL12. Using dual-color total internal reflection fluorescence microscopy and immunoprecipitation, we demonstrated that CXCR7 quickly trafficks to plasma membrane in mediating CXCL12 endocytosis and colocalizes with CXCR4 after CXCL12 treatment. Investigating the molecular mechanisms, we found that ERK1/2 endocytotic signaling pathway is essential for hNPC survival upon apoptotic challenges. Consistent with these findings, a significantly higher number of apoptotic NPCs were found in the developing brain of CXCR7 knockout mice. In conclusion, CXCL12 protects hNPCs from apoptotic challenges through CXCR7- and CXCR4-mediated endocytotic signaling. Since survival of hNPCs is important for neurogenesis, CXCR7 may become a new therapeutic target to properly regulate critical processes of brain development.
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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.