Limits...
Nogo-66 promotes the differentiation of neural progenitors into astroglial lineage cells through mTOR-STAT3 pathway.

Wang B, Xiao Z, Chen B, Han J, Gao Y, Zhang J, Zhao W, Wang X, Dai J - PLoS ONE (2008)

Bottom Line: In the present study, we have found that myelin protein and Nogo-66 promoted the differentiation of NPCs into glial lineage.These results revealed a novel function of Nogo-66 in the fate decision of NPCs.This discovery could have profound impact on the understanding of CNS development and could improve the therapy of CNS injuries.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.

ABSTRACT

Background: Neural stem/progenitor cells (NPCs) can differentiate into neurons, astrocytes and oligodendrocytes. NPCs are considered valuable for the cell therapy of injuries in the central nervous system (CNS). However, when NPCs are transplanted into the adult mammalian spinal cord, they mostly differentiate into glial lineage. The same results have been observed for endogenous NPCs during spinal cord injury. However, little is known about the mechanism of such fate decision of NPCs.

Methodology/principal findings: In the present study, we have found that myelin protein and Nogo-66 promoted the differentiation of NPCs into glial lineage. NgR and mTOR-Stat3 pathway were involved in this process. Releasing NgR from cell membranes or blocking mTOR-STAT3 could rescue the enhanced glial differentiation by Nogo-66.

Conclusions/significance: These results revealed a novel function of Nogo-66 in the fate decision of NPCs. This discovery could have profound impact on the understanding of CNS development and could improve the therapy of CNS injuries.

Show MeSH

Related in: MedlinePlus

The differentiation of NPCs treated by Myelin and MBP, respectively.(A) The immunostaining images of NPCs treated by myelin and MBP. (B) The result of a β III tubulin antibody immunostaining in NPCs exposure to myelin preparation for 8 days. The proportion of positive cells was 32.35±1.91% and 30.95±4.32% in 1.0 ug/ml and 5.0 ug/ml soluble myelin treatment respectively, significantly lower than 45.38±5.31% in 5.0 ug/ml BSA control (p<0.05).(C) The result of GFAP antibody immunostaining in NPCs exposure to myelin preparation for 8 days. The proportion of GFAP positive cells was 28.19±1.1.78% and 29.83±2.16% in 1.0 ug/ml and 5.0 ug/ml soluble myelin treatment respectively, significantly higher than 22.53±1.85% in 5.0 ug/ml BSA control (p<0.01).(D, E) Purified MBP did not affect the neural differentiation of NPCs.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2266802&req=5

pone-0001856-g002: The differentiation of NPCs treated by Myelin and MBP, respectively.(A) The immunostaining images of NPCs treated by myelin and MBP. (B) The result of a β III tubulin antibody immunostaining in NPCs exposure to myelin preparation for 8 days. The proportion of positive cells was 32.35±1.91% and 30.95±4.32% in 1.0 ug/ml and 5.0 ug/ml soluble myelin treatment respectively, significantly lower than 45.38±5.31% in 5.0 ug/ml BSA control (p<0.05).(C) The result of GFAP antibody immunostaining in NPCs exposure to myelin preparation for 8 days. The proportion of GFAP positive cells was 28.19±1.1.78% and 29.83±2.16% in 1.0 ug/ml and 5.0 ug/ml soluble myelin treatment respectively, significantly higher than 22.53±1.85% in 5.0 ug/ml BSA control (p<0.01).(D, E) Purified MBP did not affect the neural differentiation of NPCs.

Mentions: We have prepared myelin from adult rat spinal cord and assessed its effect on the differentiation of NPCs (see Fig 1B). After treated with 1.0 or 5.0 ug/ml myelin, NPCs were inhibited to differentiate into neuronal cells (β III tubulin positive cells) and promoted to differentiate into astrocytes (GFAP positive cells) (See Fig 2B and C). There are many components in myelin. We wonder if the major myelin components have the similar effects. Myelin basic protein (MBP) is one of the major myelin proteins, making up 40% of total myelin protein in CNS. We found that MBP protein did not regulate the glial and neuronal differentiation of NPCs (See Fig 2D and E). Some myelin proteins such as Nogo-A, MAG, and OMgp are axon outgrowth inhibitors in CNS. We have hypothesized that these axon inhibitory myelin proteins could mediate the NPCs fate decision. Central to the current understanding of axon inhibitors is the membrane protein Nogo-A. In the myelin preparation, Nogo-A protein was successfully detected by western blot analysis with a Nogo-A antibody (See Fig 1B).


Nogo-66 promotes the differentiation of neural progenitors into astroglial lineage cells through mTOR-STAT3 pathway.

Wang B, Xiao Z, Chen B, Han J, Gao Y, Zhang J, Zhao W, Wang X, Dai J - PLoS ONE (2008)

The differentiation of NPCs treated by Myelin and MBP, respectively.(A) The immunostaining images of NPCs treated by myelin and MBP. (B) The result of a β III tubulin antibody immunostaining in NPCs exposure to myelin preparation for 8 days. The proportion of positive cells was 32.35±1.91% and 30.95±4.32% in 1.0 ug/ml and 5.0 ug/ml soluble myelin treatment respectively, significantly lower than 45.38±5.31% in 5.0 ug/ml BSA control (p<0.05).(C) The result of GFAP antibody immunostaining in NPCs exposure to myelin preparation for 8 days. The proportion of GFAP positive cells was 28.19±1.1.78% and 29.83±2.16% in 1.0 ug/ml and 5.0 ug/ml soluble myelin treatment respectively, significantly higher than 22.53±1.85% in 5.0 ug/ml BSA control (p<0.01).(D, E) Purified MBP did not affect the neural differentiation of NPCs.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2266802&req=5

pone-0001856-g002: The differentiation of NPCs treated by Myelin and MBP, respectively.(A) The immunostaining images of NPCs treated by myelin and MBP. (B) The result of a β III tubulin antibody immunostaining in NPCs exposure to myelin preparation for 8 days. The proportion of positive cells was 32.35±1.91% and 30.95±4.32% in 1.0 ug/ml and 5.0 ug/ml soluble myelin treatment respectively, significantly lower than 45.38±5.31% in 5.0 ug/ml BSA control (p<0.05).(C) The result of GFAP antibody immunostaining in NPCs exposure to myelin preparation for 8 days. The proportion of GFAP positive cells was 28.19±1.1.78% and 29.83±2.16% in 1.0 ug/ml and 5.0 ug/ml soluble myelin treatment respectively, significantly higher than 22.53±1.85% in 5.0 ug/ml BSA control (p<0.01).(D, E) Purified MBP did not affect the neural differentiation of NPCs.
Mentions: We have prepared myelin from adult rat spinal cord and assessed its effect on the differentiation of NPCs (see Fig 1B). After treated with 1.0 or 5.0 ug/ml myelin, NPCs were inhibited to differentiate into neuronal cells (β III tubulin positive cells) and promoted to differentiate into astrocytes (GFAP positive cells) (See Fig 2B and C). There are many components in myelin. We wonder if the major myelin components have the similar effects. Myelin basic protein (MBP) is one of the major myelin proteins, making up 40% of total myelin protein in CNS. We found that MBP protein did not regulate the glial and neuronal differentiation of NPCs (See Fig 2D and E). Some myelin proteins such as Nogo-A, MAG, and OMgp are axon outgrowth inhibitors in CNS. We have hypothesized that these axon inhibitory myelin proteins could mediate the NPCs fate decision. Central to the current understanding of axon inhibitors is the membrane protein Nogo-A. In the myelin preparation, Nogo-A protein was successfully detected by western blot analysis with a Nogo-A antibody (See Fig 1B).

Bottom Line: In the present study, we have found that myelin protein and Nogo-66 promoted the differentiation of NPCs into glial lineage.These results revealed a novel function of Nogo-66 in the fate decision of NPCs.This discovery could have profound impact on the understanding of CNS development and could improve the therapy of CNS injuries.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.

ABSTRACT

Background: Neural stem/progenitor cells (NPCs) can differentiate into neurons, astrocytes and oligodendrocytes. NPCs are considered valuable for the cell therapy of injuries in the central nervous system (CNS). However, when NPCs are transplanted into the adult mammalian spinal cord, they mostly differentiate into glial lineage. The same results have been observed for endogenous NPCs during spinal cord injury. However, little is known about the mechanism of such fate decision of NPCs.

Methodology/principal findings: In the present study, we have found that myelin protein and Nogo-66 promoted the differentiation of NPCs into glial lineage. NgR and mTOR-Stat3 pathway were involved in this process. Releasing NgR from cell membranes or blocking mTOR-STAT3 could rescue the enhanced glial differentiation by Nogo-66.

Conclusions/significance: These results revealed a novel function of Nogo-66 in the fate decision of NPCs. This discovery could have profound impact on the understanding of CNS development and could improve the therapy of CNS injuries.

Show MeSH
Related in: MedlinePlus