ArticleStem cells (Dayton, Ohio)2012
IGF-II promotes stemness of neural restricted precursors.
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 57 papers.
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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.
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Who cites it
57 citing papers in PubMed, 86 citations in OpenAlex.
- Review
- Multi-tissue transcriptomic aging atlas reveals predictive aging biomarkers in the killifish.Nature aging · 2026Article
- Serum Insulin-like Growth Factor-II Is Associated with Poor Poststroke Outcomes in Males: A Secondary Analysis.International journal of molecular sciences · 2025Article
- IGFBP-2 and IGF-II: Key Components of the Neural Stem Cell Niche? Implications for Glioblastoma Pathogenesis.International journal of molecular sciences · 2025Review
- Insulin-Like Growth Factor Signaling in Alzheimer's Disease: Pathophysiology and Therapeutic Strategies.Molecular neurobiology · 2025Review
- The role of IGF/IGF-1R signaling in the regulation of cancer stem cells.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024Review
- The Role of PLAG1 in Mouse Brain Development and Neurogenesis.Molecular neurobiology · 2024Article
- Autocrine insulin-like growth factor 2 signaling as a potential target in the associated development of pulmonary emphysema and cancer in smokers.Inflammation and regeneration · 2024Article
- Role of insulin-like growth factor-2 in Alzheimer's disease induced memory impairment and underlying mechanisms.Frontiers in cellular neuroscience · 2024Review
- Insulin signaling in development.Development (Cambridge, England) · 2023Article
- Insulin-like growth factor-2 is a promising candidate for the treatment and prevention of Alzheimer's disease.CNS neuroscience & therapeutics · 2023Review
- Cell cycle control by the insulin-like growth factor signal: at the crossroad between cell growth and mitotic regulation.Cell cycle (Georgetown, Tex.) · 2023Review
- Insulin-like Growth Factor-2 (IGF-2) in Fibrosis.Biomolecules · 2022Review
- Subventricular zone adult mouse neural stem cells require insulin receptor for self-renewal.Stem cell reports · 2022Article
- Mini review: The relationship between energy status and adult hippocampal neurogenesis.Neuroscience letters · 2021Review
- Insulin-like growth factors: Ligands, binding proteins, and receptors.Molecular metabolism · 2021Review
- OTX2 Homeoprotein Functions in Adult Choroid Plexus.International journal of molecular sciences · 2021Article
- Insulin-like growth factor 2-enhanced osteogenic differentiation of stem cell spheroids by regulation of Runx2 and Col1 expression.Experimental and therapeutic medicine · 2021Article
- Brain Insulin Resistance: Focus on Insulin Receptor-Mitochondria Interactions.Life (Basel, Switzerland) · 2021Review
- Insulin-Like Growth Factor 2 As a Possible Neuroprotective Agent and Memory Enhancer-Its Comparative Expression, Processing and Signaling in Mammalian CNS.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Insulin-like growth factor (IGF)-I and IGF-II regulate brain development and growth through the IGF type 1 receptor (IGF-1R). Less appreciated is that IGF-II, but not IGF-I, activates a splice variant of the insulin receptor (IR) known as IR-A. We hypothesized that IGF-II exerts distinct effects from IGF-I on neural stem/progenitor cells (NSPs) via its interaction with IR-A. Immunofluorescence revealed high IGF-II in the medial region of the subventricular zone (SVZ) comprising the neural stem cell niche, with IGF-II mRNA predominant in the adjacent choroid plexus. The IGF-1R and the IR isoforms were differentially expressed with IR-A predominant in the medial SVZ, whereas the IGF-1R was more abundant laterally. Similarly, IR-A was more highly expressed by NSPs, whereas the IGF-1R was more highly expressed by lineage restricted cells. In vitro, IGF-II was more potent in promoting NSP expansion than either IGF-I or standard growth medium. Limiting dilution and differentiation assays revealed that IGF-II was superior to IGF-I in promoting stemness. In vivo, NSPs propagated in IGF-II migrated to and took up residence in periventricular niches while IGF-I-treated NSPs predominantly colonized white matter. Knockdown of IR or IGF-1R using shRNAs supported the conclusion that the IGF-1R promotes progenitor proliferation, whereas the IR is important for self-renewal. Q-PCR revealed that IGF-II increased Oct4, Sox1, and FABP7 mRNA levels in NSPs. Our data support the conclusion that IGF-II promotes the self-renewal of neural stem/progenitors via the IR. By contrast, IGF-1R functions as a mitogenic receptor to increase precursor abundance.
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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.