PT - JOURNAL ARTICLE AU - Carlos Vicario-Abejón AU - Marı́a J. Yusta-Boyo AU - Carmen Fernández-Moreno AU - Flora de Pablo TI - Locally Born Olfactory Bulb Stem Cells Proliferate in Response to Insulin-Related Factors and Require Endogenous Insulin-Like Growth Factor-I for Differentiation into Neurons and Glia AID - 10.1523/JNEUROSCI.23-03-00895.2003 DP - 2003 Feb 01 TA - The Journal of Neuroscience PG - 895--906 VI - 23 IP - 3 4099 - http://www.jneurosci.org/content/23/3/895.short 4100 - http://www.jneurosci.org/content/23/3/895.full SO - J. Neurosci.2003 Feb 01; 23 AB - After late embryogenesis, new neurons are continuously added to the olfactory bulb (OB) from stem cells located in the forebrain subventricular zone. Nonetheless, stem cells have not been described within the embryonic olfactory bulb. Here we report the isolation of local olfactory bulb stem cells from the embryonic day 12.5–14.5 mouse embryo. These cells were 99.2% nestin positive and proliferated extensively in culture to at least 150 cell doublings. Clonal analysis demonstrated that neurons (TuJ1+), astrocytes (GFAP+), and oligodendrocytes (O4+) could be generated from single-plated cells, indicating that they are multipotent. At least 90% of proliferating cells expressed insulin-like growth factor-I (IGF-I), (pro)insulin, and their cognate receptors; these growth factors collaborated with fibroblast growth factor-2 plus epidermal growth factor (EGF) to promote stem cell proliferation and sphere formation. Cells fromIgf-I−/−mice, however, proliferated as extensively as didIgf-I+/+ cells. Differentiation and survival of stem cell-generated neurons and glia showed strong dependence on exogenous IGF-I, but oligodendrocyte differentiation also required insulin at low concentration. Furthermore, the percentages of stem cell-generated neurons, astrocytes, and oligodendrocytes were markedly lower in the cultures prepared from theIgf-I−/−mice compared with those ofIgf-I+/+. Concordantly, lack of IGF-I resulted in abnormal formation of the olfactory bulb mitral cell layer and altered radial glia morphology. These results support the presence within the embryonic mouse olfactory bulb of stem cells with specific requirements for insulin-related growth factors for proliferation or differentiation. They demonstrate that IGF-I is an endogenous factor regulating the differentiation of stem and other precursor cells within the olfactory bulb.