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Cholera toxin regulates a signaling pathway critical for the expansion of neural stem cell cultures from the fetal and adult rodent brains.

Androutsellis-Theotokis A, Walbridge S, Park DM, Lonser RR, McKay RD - PLoS ONE (2010)

Bottom Line: Here we show that Cholera toxin regulates two recently characterized NSC markers, the Tie2 receptor and the transcription factor Hes3, and promotes the expansion of NSCs in culture.Cholera toxin increases immunoreactivity for the Tie2 receptor and rapidly induces the nuclear localization of Hes3.This is followed by powerful cultured NSC expansion and induction of proliferation both in the presence and absence of mitogen.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Molecular Biology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA. AndreasTheotokis@gmail.com

ABSTRACT

Background: New mechanisms that regulate neural stem cell (NSC) expansion will contribute to improved assay systems and the emerging regenerative approach that targets endogenous stem cells. Expanding knowledge on the control of stem cell self renewal will also lead to new approaches for targeting the stem cell population of cancers.

Methodology/principal findings: Here we show that Cholera toxin regulates two recently characterized NSC markers, the Tie2 receptor and the transcription factor Hes3, and promotes the expansion of NSCs in culture. Cholera toxin increases immunoreactivity for the Tie2 receptor and rapidly induces the nuclear localization of Hes3. This is followed by powerful cultured NSC expansion and induction of proliferation both in the presence and absence of mitogen.

Conclusions/significance: Our data suggest a new cell biological mechanism that regulates the self renewal and differentiation properties of stem cells, providing a new logic to manipulate NSCs in the context of regenerative disease and cancer.

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Related in: MedlinePlus

Cholera toxin cooperates with pro-survival factors to expand NSC numbers in vitro.CT and ChAB co-operate to increase fetal NSC numbers (5-day treatment).
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pone-0010841-g006: Cholera toxin cooperates with pro-survival factors to expand NSC numbers in vitro.CT and ChAB co-operate to increase fetal NSC numbers (5-day treatment).

Mentions: We have previously reported a pharmacological treatment that promotes the survival and expansion of fetal and adult NSCs in culture and of adult neural precursors in vivo [25]. This combined treatment (CT) contains the Tie2 ligand Ang2, the Notch ligand Dll4, a JAK kinase inhibitor, and insulin. In these experiments, insulin is contained in the culture medium throughout their duration. We investigated whether the pro-expansion capabilities of CT and CholAB can be combined to establish a new treatment that will maximize NSC number increase. We found that CT and CholAB co-operate to increase mouse fetal NSC numbers in cultures grown for 5 days in the presence of FGF2 (Figure 6). These results show that a combination of pharmacological treatments that affect signal transduction and cell biological processes can greatly enhance the efficiency of primary cell culture.


Cholera toxin regulates a signaling pathway critical for the expansion of neural stem cell cultures from the fetal and adult rodent brains.

Androutsellis-Theotokis A, Walbridge S, Park DM, Lonser RR, McKay RD - PLoS ONE (2010)

Cholera toxin cooperates with pro-survival factors to expand NSC numbers in vitro.CT and ChAB co-operate to increase fetal NSC numbers (5-day treatment).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2877108&req=5

pone-0010841-g006: Cholera toxin cooperates with pro-survival factors to expand NSC numbers in vitro.CT and ChAB co-operate to increase fetal NSC numbers (5-day treatment).
Mentions: We have previously reported a pharmacological treatment that promotes the survival and expansion of fetal and adult NSCs in culture and of adult neural precursors in vivo [25]. This combined treatment (CT) contains the Tie2 ligand Ang2, the Notch ligand Dll4, a JAK kinase inhibitor, and insulin. In these experiments, insulin is contained in the culture medium throughout their duration. We investigated whether the pro-expansion capabilities of CT and CholAB can be combined to establish a new treatment that will maximize NSC number increase. We found that CT and CholAB co-operate to increase mouse fetal NSC numbers in cultures grown for 5 days in the presence of FGF2 (Figure 6). These results show that a combination of pharmacological treatments that affect signal transduction and cell biological processes can greatly enhance the efficiency of primary cell culture.

Bottom Line: Here we show that Cholera toxin regulates two recently characterized NSC markers, the Tie2 receptor and the transcription factor Hes3, and promotes the expansion of NSCs in culture.Cholera toxin increases immunoreactivity for the Tie2 receptor and rapidly induces the nuclear localization of Hes3.This is followed by powerful cultured NSC expansion and induction of proliferation both in the presence and absence of mitogen.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Molecular Biology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA. AndreasTheotokis@gmail.com

ABSTRACT

Background: New mechanisms that regulate neural stem cell (NSC) expansion will contribute to improved assay systems and the emerging regenerative approach that targets endogenous stem cells. Expanding knowledge on the control of stem cell self renewal will also lead to new approaches for targeting the stem cell population of cancers.

Methodology/principal findings: Here we show that Cholera toxin regulates two recently characterized NSC markers, the Tie2 receptor and the transcription factor Hes3, and promotes the expansion of NSCs in culture. Cholera toxin increases immunoreactivity for the Tie2 receptor and rapidly induces the nuclear localization of Hes3. This is followed by powerful cultured NSC expansion and induction of proliferation both in the presence and absence of mitogen.

Conclusions/significance: Our data suggest a new cell biological mechanism that regulates the self renewal and differentiation properties of stem cells, providing a new logic to manipulate NSCs in the context of regenerative disease and cancer.

Show MeSH
Related in: MedlinePlus