Stromal cell-secreted factors promote the survival of embryonic stem cell-derived early neural stem/progenitor cells via the activation of MAPK and PI3K-Akt pathways

Seiji Ishii, Yohei Okada, Toshihiko Kadoya, Yumi Matsuzaki, Takuya Shimazaki, Hideyuki Okano

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Neural stem/progenitor cells (NS/PCs) have been studied extensively with the hope of using them clinically to repair the damaged central nervous system. However, little is known about the signals that regulate the proliferation, survival, and differentiation of NS/PCs in early development. To clarify the underlying mechanisms, we took advantage of an in vitro ES cell differentiation system from which we can obtain neurospheres containing NS/PCs with characteristics of the early caudal neural tube, by treating embryoid bodies (EBs) with a low concentration of retinoic acid (RA). We found that conditioned medium from the PA6 stromal cell line (PA6CM) increased the efficiency of neurosphere formation by suppressing apoptosis and promoting the survival of the NS/PCs. PA6CM also induced the phosphorylation of Erk1/2 and Akt1 in cells derived from the EBs. Furthermore, inhibitors of the MAPK and PI3K-Akt signaling pathways, U0126 and LY294002, attenuated the effects of PA6CM, significantly increasing the number of apoptotic cells and decreasing the number of viable cells among the ES cell-derived NS/PCs. Thus, PA6CM appears to contain soluble factors that promote the survival of ES cell-derived early NS/PCs through the activation of the MAPK and PI3K-Akt pathways.

Original languageEnglish
Pages (from-to)722-734
Number of pages13
JournalJournal of Neuroscience Research
Volume88
Issue number4
DOIs
Publication statusPublished - 2010 Mar

Fingerprint

Neural Stem Cells
Embryonic Stem Cells
Stromal Cells
Phosphatidylinositol 3-Kinases
Stem Cells
Embryoid Bodies
Neural Tube
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Conditioned Culture Medium
Tretinoin
Cell Differentiation
Cell Survival
Central Nervous System
Cell Count
Phosphorylation
Apoptosis
Cell Line

Keywords

  • ES cells
  • Neural stem/progenitor cells
  • Signal transduction
  • Stromal cells
  • Survival

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

Cite this

Stromal cell-secreted factors promote the survival of embryonic stem cell-derived early neural stem/progenitor cells via the activation of MAPK and PI3K-Akt pathways. / Ishii, Seiji; Okada, Yohei; Kadoya, Toshihiko; Matsuzaki, Yumi; Shimazaki, Takuya; Okano, Hideyuki.

In: Journal of Neuroscience Research, Vol. 88, No. 4, 03.2010, p. 722-734.

Research output: Contribution to journalArticle

@article{d42d96cb752f4472b8f4973e921c8a6f,
title = "Stromal cell-secreted factors promote the survival of embryonic stem cell-derived early neural stem/progenitor cells via the activation of MAPK and PI3K-Akt pathways",
abstract = "Neural stem/progenitor cells (NS/PCs) have been studied extensively with the hope of using them clinically to repair the damaged central nervous system. However, little is known about the signals that regulate the proliferation, survival, and differentiation of NS/PCs in early development. To clarify the underlying mechanisms, we took advantage of an in vitro ES cell differentiation system from which we can obtain neurospheres containing NS/PCs with characteristics of the early caudal neural tube, by treating embryoid bodies (EBs) with a low concentration of retinoic acid (RA). We found that conditioned medium from the PA6 stromal cell line (PA6CM) increased the efficiency of neurosphere formation by suppressing apoptosis and promoting the survival of the NS/PCs. PA6CM also induced the phosphorylation of Erk1/2 and Akt1 in cells derived from the EBs. Furthermore, inhibitors of the MAPK and PI3K-Akt signaling pathways, U0126 and LY294002, attenuated the effects of PA6CM, significantly increasing the number of apoptotic cells and decreasing the number of viable cells among the ES cell-derived NS/PCs. Thus, PA6CM appears to contain soluble factors that promote the survival of ES cell-derived early NS/PCs through the activation of the MAPK and PI3K-Akt pathways.",
keywords = "ES cells, Neural stem/progenitor cells, Signal transduction, Stromal cells, Survival",
author = "Seiji Ishii and Yohei Okada and Toshihiko Kadoya and Yumi Matsuzaki and Takuya Shimazaki and Hideyuki Okano",
year = "2010",
month = "3",
doi = "10.1002/jnr.22250",
language = "English",
volume = "88",
pages = "722--734",
journal = "Journal of Neuroscience Research",
issn = "0360-4012",
publisher = "Wiley-Liss Inc.",
number = "4",

}

TY - JOUR

T1 - Stromal cell-secreted factors promote the survival of embryonic stem cell-derived early neural stem/progenitor cells via the activation of MAPK and PI3K-Akt pathways

AU - Ishii, Seiji

AU - Okada, Yohei

AU - Kadoya, Toshihiko

AU - Matsuzaki, Yumi

AU - Shimazaki, Takuya

AU - Okano, Hideyuki

PY - 2010/3

Y1 - 2010/3

N2 - Neural stem/progenitor cells (NS/PCs) have been studied extensively with the hope of using them clinically to repair the damaged central nervous system. However, little is known about the signals that regulate the proliferation, survival, and differentiation of NS/PCs in early development. To clarify the underlying mechanisms, we took advantage of an in vitro ES cell differentiation system from which we can obtain neurospheres containing NS/PCs with characteristics of the early caudal neural tube, by treating embryoid bodies (EBs) with a low concentration of retinoic acid (RA). We found that conditioned medium from the PA6 stromal cell line (PA6CM) increased the efficiency of neurosphere formation by suppressing apoptosis and promoting the survival of the NS/PCs. PA6CM also induced the phosphorylation of Erk1/2 and Akt1 in cells derived from the EBs. Furthermore, inhibitors of the MAPK and PI3K-Akt signaling pathways, U0126 and LY294002, attenuated the effects of PA6CM, significantly increasing the number of apoptotic cells and decreasing the number of viable cells among the ES cell-derived NS/PCs. Thus, PA6CM appears to contain soluble factors that promote the survival of ES cell-derived early NS/PCs through the activation of the MAPK and PI3K-Akt pathways.

AB - Neural stem/progenitor cells (NS/PCs) have been studied extensively with the hope of using them clinically to repair the damaged central nervous system. However, little is known about the signals that regulate the proliferation, survival, and differentiation of NS/PCs in early development. To clarify the underlying mechanisms, we took advantage of an in vitro ES cell differentiation system from which we can obtain neurospheres containing NS/PCs with characteristics of the early caudal neural tube, by treating embryoid bodies (EBs) with a low concentration of retinoic acid (RA). We found that conditioned medium from the PA6 stromal cell line (PA6CM) increased the efficiency of neurosphere formation by suppressing apoptosis and promoting the survival of the NS/PCs. PA6CM also induced the phosphorylation of Erk1/2 and Akt1 in cells derived from the EBs. Furthermore, inhibitors of the MAPK and PI3K-Akt signaling pathways, U0126 and LY294002, attenuated the effects of PA6CM, significantly increasing the number of apoptotic cells and decreasing the number of viable cells among the ES cell-derived NS/PCs. Thus, PA6CM appears to contain soluble factors that promote the survival of ES cell-derived early NS/PCs through the activation of the MAPK and PI3K-Akt pathways.

KW - ES cells

KW - Neural stem/progenitor cells

KW - Signal transduction

KW - Stromal cells

KW - Survival

UR - http://www.scopus.com/inward/record.url?scp=76549088500&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=76549088500&partnerID=8YFLogxK

U2 - 10.1002/jnr.22250

DO - 10.1002/jnr.22250

M3 - Article

VL - 88

SP - 722

EP - 734

JO - Journal of Neuroscience Research

JF - Journal of Neuroscience Research

SN - 0360-4012

IS - 4

ER -