Erythropoietin Regulates the In Vitro and In Vivo Production of Neuronal Progenitors by Mammalian Forebrain Neural Stem Cells
By T. Shingo, S. T. Sorokan, T. Shimazaki, S. Weiss. Journal of Neuroscience, 2001
692 citations recorded by the source corpus.
Recent studies have shown that neurogenesis is enhanced after hypoxia and that erythropoietin (EPO), an inducible cytokine, is produced in the brain as part of the intrinsic hypoxia response. Thus, we asked whether EPO might regulate neurogenesis by forebrain neural stem cells (NSCs). We found that EPO receptors are expressed in the embryonic germinal zone during neurogenesis as well as in the adult subventricular zone, which continues to generate neurons throughout adulthood. Cultured NSCs exposed to a modest hypoxia produced two- to threefold more neurons, which was associated with an elevation in EPO gene expression. The enhanced neuron production attributable to hypoxia was mimicked by EPO and blocked by coadministration of an EPO neutralizing antibody. EPO appears to act directly on NSCs, promoting the production of neuronal progenitors at the expense of multipotent progenitors. EPO infusion into the adult lateral ventricles resulted in a decrease in the numbers of NSCs in the subventricular zone, an increase in newly generated cells migrating to the olfactory bulb, and an increase in new olfactory bulb interneurons. Infusion of anti-EPO antibodies had the opposite effect: an increase in the number of NSCs in the subventricular zone and a decrease in the number of newly generated cells migrating to the bulb. These findings suggest that EPO is an autocrine–paracrine factor, capable of regulating the production of neuronal progenitor cells by forebrain NSCs.
Subfields: Developmental Neuroscience, Genetics
View Paper: https://www.semanticscholar.org/paper/8f80c903629a73de5b001a73f8f42e8567d5d513
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Citations in the corpus
- Oxygen in stem cell biology: a critical component of the stem cell niche. (2010, background): “This pathway also increases the expression of Mash1, a transcription factor that directs NSCs toward a neuronal lineage (Shingo et al., 2001).”
- Adult neurogenesis: from precursors to network and physiology. (2005, background): “poietin (507) and the recently discovered “stem cell fac-”
- Cellular and molecular mechanisms of neural repair after stroke: Making waves (2006, background): “In vitro evidence suggests that EPO promotes neuronal differentiation of neural stem cells.(75,76) Pharmacological doses of EPO promote cell division and increased neuronal progenitor cells in the SVZ after stroke.”