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An Fgfr3-iCreER(T2) transgenic mouse line for studies of neural stem cells and astrocytes.

ABSTRACT: The lack of markers for astrocytes, particularly gray matter astrocytes, significantly hinders research into their development and physiological properties. We previously reported that fibroblast growth factor receptor 3 (Fgfr3) is expressed by radial precursors in the ventricular zone of the embryonic neural tube and subsequently by differentiated astrocytes in gray and white matter. Here, we describe an Fgfr3-iCreER(T2) phage artificial chromosome transgenic mouse line that allows efficient tamoxifen-induced Cre recombination in Fgfr3-expressing cells, including radial glial cells in the embryonic neural tube and both fibrous and protoplasmic astrocytes in the mature central nervous system. This mouse strain will therefore be useful for studies of normal astrocyte biology and their responses to CNS injury or disease. In addition, Fgfr3-iCreER(T2) drives Cre recombination in all neurosphere-forming stem cells in the adult spinal cord and at least 90% of those in the adult forebrain subventricular zone. We made use of this to show that there is continuous accumulation of all major interneuron subtypes in the olfactory bulb (OB) from postnatal day 50 (P50) until at least P230 ( approximately 8 months of age). It therefore seems likely that adult-born interneurons integrate into existing circuitry and perform long-term functions in the adult OB.

SUBMITTER: Young KM

PROVIDER: S-EPMC6329446 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature

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An Fgfr3-iCreER(T2) transgenic mouse line for studies of neural stem cells and astrocytes.

Young Kaylene M KM Mitsumori Tomoyuki T Pringle Nigel N Grist Matthew M Kessaris Nicoletta N Richardson William D WD

Glia 20100601 8

The lack of markers for astrocytes, particularly gray matter astrocytes, significantly hinders research into their development and physiological properties. We previously reported that fibroblast growth factor receptor 3 (Fgfr3) is expressed by radial precursors in the ventricular zone of the embryonic neural tube and subsequently by differentiated astrocytes in gray and white matter. Here, we describe an Fgfr3-iCreER(T2) phage artificial chromosome transgenic mouse line that allows efficient ta ...[more]

PMID: 20155815

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Project description:Exosomes appear to be effective inter-cellular communicators delivering several types of molecules, such as proteins and RNAs, suggesting that they could influence neural stem cell (NSC) differentiation. Our RNA sequencing studies demonstrated that the RNAs related to cell proliferation and astrocyte differentiation were upregulated in human mesenchymal stem cells (hMSC) when co-cultured with exosomes obtained from the culture medium of human glioma cells (U87). Metallothionein 3 and elastin genes, which are related to cell proliferation, increased 10 and 7.2 fold, respectively. Expression of genes for astrocyte differentiation, such as tumor growth factor alpha, induced protein 3 of the NOTCH1 family, colony stimulating factor and interleukin 6 of the STAT3 family and Hes family bHLH transcription factor 1 also increased by 2.3, 10, 4.7 and 2.9 fold, respectively. We further examined the effects of these exosomes on rat fetal neural stem cell (rNSC) differentiation using the secreted exosomes from U87 glioma cells or exosomes from U87 cells that were stimulated with interleukin 1? (IL-1?). The rNSCs, extracted from rat brains at embryonic day 14 (E14), underwent a culture protocol that normally leads to predominant (~90%) differentiation to ODCs. However, in the presence of the exosomes from untreated or IL-1?-treated U87 cells, significantly more cells differentiated into astrocytes, especially in the presence of exosomes obtained from the IL-1?-challenged glioma cells. Moreover, glioma-derived exosomes appeared to inhibit rNSC differentiation into ODCs or astrocytes as indicated by a significantly increased population of unlabeled cells. A portion of the resulting astrocytes co-expressed both CD133 and glial fibrillary acidic protein (GFAP) suggesting that exosomes from U87 cells could promote astrocytic differentiation of NSCs with features expected from a transformed cell. Our data clearly demonstrated that exosomes secreted by human glioma cells provide a strong driving force for rat neural stem cells to differentiate into astrocytes, uncovering potential pathways and therapeutic targets that might control this aggressive tumor type.

Dataset Information

An Fgfr3-iCreER(T2) transgenic mouse line for studies of neural stem cells and astrocytes.

Publications

An Fgfr3-iCreER(T2) transgenic mouse line for studies of neural stem cells and astrocytes.

Similar Datasets

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