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IGF-I instructs multipotent adult neural progenitor cells to become oligodendrocytes.

Hsieh J, Aimone JB, Kaspar BK, Kuwabara T, Nakashima K, Gage FH - J. Cell Biol. (2004)

Bottom Line: Oligodendrocyte differentiation by IGF-I appears to be mediated through an inhibition of bone morphogenetic protein signaling.Furthermore, overexpression of IGF-I in the hippocampus leads to an increase in oligodendrocyte markers.These data demonstrate the existence of a single molecule, IGF-I, that can influence the fate choice of multipotent adult neural progenitor cells to an oligodendroglial lineage.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Genetics, The Salk Institute, 10010 N. Torrey Pines Road, La Jolla, CA 92037, USA.

ABSTRACT
Adult multipotent neural progenitor cells can differentiate into neurons, astrocytes, and oligodendrocytes in the mammalian central nervous system, but the molecular mechanisms that control their differentiation are not yet well understood. Insulin-like growth factor I (IGF-I) can promote the differentiation of cells already committed to an oligodendroglial lineage during development. However, it is unclear whether IGF-I affects multipotent neural progenitor cells. Here, we show that IGF-I stimulates the differentiation of multipotent adult rat hippocampus-derived neural progenitor cells into oligodendrocytes. Modeling analysis indicates that the actions of IGF-I are instructive. Oligodendrocyte differentiation by IGF-I appears to be mediated through an inhibition of bone morphogenetic protein signaling. Furthermore, overexpression of IGF-I in the hippocampus leads to an increase in oligodendrocyte markers. These data demonstrate the existence of a single molecule, IGF-I, that can influence the fate choice of multipotent adult neural progenitor cells to an oligodendroglial lineage.

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IGF-I overexpression in the hilus promotes oligodendrocyte differentiation in vivo. (A–J) Representative images of brain sections focusing in on the hilar region in animals injected with rAAV-β-gal controls (A–D and I) and rAAV-IGF-I (E–H and J). Sections were triple labeled with antibodies to oligodendrocyte markers RIP (A and E) and MBP (B and F), and an astrocyte marker GFAP (C and G). Merged images are shown in D and H; RIP is in red, MBP is in blue, GFAP is in green. (I and J) Representative sections stained with the oligodendrocyte marker GST-π in red and DAPI to visualize cell nuclei. White arrows indicate cells that are GST-π–positive. (K) The average number of cells in the hilus (in three adjacent fields distal to the injection site) per section in which GST-π was detected in each animal group (rAAV-β-gal animals, n = 3; rAAV-IGF-I animals, n = 4) is plotted. The asterisk indicates that values are significantly different between control and IGF-I–overexpressed animals (P < 0.001, t test), and error bars represent SDs. Bar, 100 μm.
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fig7: IGF-I overexpression in the hilus promotes oligodendrocyte differentiation in vivo. (A–J) Representative images of brain sections focusing in on the hilar region in animals injected with rAAV-β-gal controls (A–D and I) and rAAV-IGF-I (E–H and J). Sections were triple labeled with antibodies to oligodendrocyte markers RIP (A and E) and MBP (B and F), and an astrocyte marker GFAP (C and G). Merged images are shown in D and H; RIP is in red, MBP is in blue, GFAP is in green. (I and J) Representative sections stained with the oligodendrocyte marker GST-π in red and DAPI to visualize cell nuclei. White arrows indicate cells that are GST-π–positive. (K) The average number of cells in the hilus (in three adjacent fields distal to the injection site) per section in which GST-π was detected in each animal group (rAAV-β-gal animals, n = 3; rAAV-IGF-I animals, n = 4) is plotted. The asterisk indicates that values are significantly different between control and IGF-I–overexpressed animals (P < 0.001, t test), and error bars represent SDs. Bar, 100 μm.

Mentions: Our findings raised the question of whether IGF-I also has effects on oligodendrocyte differentiation in vivo in the region where adult hippocampal neural progenitor cells normally reside. Therefore, we used adeno-associated virus (AAV) to overexpress IGF-I in the adult rat hippocampus. To evaluate effects on the endogenous oligodendrocyte population due to IGF-I overexpression in vivo, we used the oligodendrocyte marker RIP. We focused our analyses on the hilar region of the dentate gyrus because there is a higher concentration of oligodendrocytes in this region. An increase of RIP staining in the hilus of rAAV-IGF-I–infected animals compared with rAAV-β-gal–infected controls was apparent (Fig. 7, A and E). Quantification of RIP immunofluorescence in the hilus of rAAV-β-gal–infected control animals resulted in an average pixel intensity of 45.49 ± 2.01 (n = 3 rats), compared with an average pixel intensity of 99.95 ± 18.27 (n = 4 rats) in rAAV-IGF-I–infected animals (P < 0.05, t test). Similar results were seen in at least three adjacent fields of the same section.


IGF-I instructs multipotent adult neural progenitor cells to become oligodendrocytes.

Hsieh J, Aimone JB, Kaspar BK, Kuwabara T, Nakashima K, Gage FH - J. Cell Biol. (2004)

IGF-I overexpression in the hilus promotes oligodendrocyte differentiation in vivo. (A–J) Representative images of brain sections focusing in on the hilar region in animals injected with rAAV-β-gal controls (A–D and I) and rAAV-IGF-I (E–H and J). Sections were triple labeled with antibodies to oligodendrocyte markers RIP (A and E) and MBP (B and F), and an astrocyte marker GFAP (C and G). Merged images are shown in D and H; RIP is in red, MBP is in blue, GFAP is in green. (I and J) Representative sections stained with the oligodendrocyte marker GST-π in red and DAPI to visualize cell nuclei. White arrows indicate cells that are GST-π–positive. (K) The average number of cells in the hilus (in three adjacent fields distal to the injection site) per section in which GST-π was detected in each animal group (rAAV-β-gal animals, n = 3; rAAV-IGF-I animals, n = 4) is plotted. The asterisk indicates that values are significantly different between control and IGF-I–overexpressed animals (P < 0.001, t test), and error bars represent SDs. Bar, 100 μm.
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Related In: Results  -  Collection

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fig7: IGF-I overexpression in the hilus promotes oligodendrocyte differentiation in vivo. (A–J) Representative images of brain sections focusing in on the hilar region in animals injected with rAAV-β-gal controls (A–D and I) and rAAV-IGF-I (E–H and J). Sections were triple labeled with antibodies to oligodendrocyte markers RIP (A and E) and MBP (B and F), and an astrocyte marker GFAP (C and G). Merged images are shown in D and H; RIP is in red, MBP is in blue, GFAP is in green. (I and J) Representative sections stained with the oligodendrocyte marker GST-π in red and DAPI to visualize cell nuclei. White arrows indicate cells that are GST-π–positive. (K) The average number of cells in the hilus (in three adjacent fields distal to the injection site) per section in which GST-π was detected in each animal group (rAAV-β-gal animals, n = 3; rAAV-IGF-I animals, n = 4) is plotted. The asterisk indicates that values are significantly different between control and IGF-I–overexpressed animals (P < 0.001, t test), and error bars represent SDs. Bar, 100 μm.
Mentions: Our findings raised the question of whether IGF-I also has effects on oligodendrocyte differentiation in vivo in the region where adult hippocampal neural progenitor cells normally reside. Therefore, we used adeno-associated virus (AAV) to overexpress IGF-I in the adult rat hippocampus. To evaluate effects on the endogenous oligodendrocyte population due to IGF-I overexpression in vivo, we used the oligodendrocyte marker RIP. We focused our analyses on the hilar region of the dentate gyrus because there is a higher concentration of oligodendrocytes in this region. An increase of RIP staining in the hilus of rAAV-IGF-I–infected animals compared with rAAV-β-gal–infected controls was apparent (Fig. 7, A and E). Quantification of RIP immunofluorescence in the hilus of rAAV-β-gal–infected control animals resulted in an average pixel intensity of 45.49 ± 2.01 (n = 3 rats), compared with an average pixel intensity of 99.95 ± 18.27 (n = 4 rats) in rAAV-IGF-I–infected animals (P < 0.05, t test). Similar results were seen in at least three adjacent fields of the same section.

Bottom Line: Oligodendrocyte differentiation by IGF-I appears to be mediated through an inhibition of bone morphogenetic protein signaling.Furthermore, overexpression of IGF-I in the hippocampus leads to an increase in oligodendrocyte markers.These data demonstrate the existence of a single molecule, IGF-I, that can influence the fate choice of multipotent adult neural progenitor cells to an oligodendroglial lineage.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Genetics, The Salk Institute, 10010 N. Torrey Pines Road, La Jolla, CA 92037, USA.

ABSTRACT
Adult multipotent neural progenitor cells can differentiate into neurons, astrocytes, and oligodendrocytes in the mammalian central nervous system, but the molecular mechanisms that control their differentiation are not yet well understood. Insulin-like growth factor I (IGF-I) can promote the differentiation of cells already committed to an oligodendroglial lineage during development. However, it is unclear whether IGF-I affects multipotent neural progenitor cells. Here, we show that IGF-I stimulates the differentiation of multipotent adult rat hippocampus-derived neural progenitor cells into oligodendrocytes. Modeling analysis indicates that the actions of IGF-I are instructive. Oligodendrocyte differentiation by IGF-I appears to be mediated through an inhibition of bone morphogenetic protein signaling. Furthermore, overexpression of IGF-I in the hippocampus leads to an increase in oligodendrocyte markers. These data demonstrate the existence of a single molecule, IGF-I, that can influence the fate choice of multipotent adult neural progenitor cells to an oligodendroglial lineage.

Show MeSH
Related in: MedlinePlus