Potentiation of astrogliogenesis by STAT3-mediated activation of bone morphogenetic protein-Smad signaling in neural stem cells

Shinji Fukuda, Masahiko Abematsu, Hiroyuki Mori, Makoto Yanagisawa, Tetsushi Kagawa, Kinichi Nakashima, Akihiko Yoshimura, Tetsuya Taga

Research output: Contribution to journalArticle

92 Citations (Scopus)

Abstract

Astrocytes play important roles in brain development and injury response. Transcription factors STAT3 and Smadl, activated by leukemia inhibitory factor (LIF) and bone morphogenetic protein 2 (BMP2), respectively, form a complex with the coactivator p300 to synergistically induce astrocytes from neuroepithelial cells (NECs) (K. Nakashima, M. Yanagisawa, H. Arakawa, N. Kimura, T. Hisatsune, M. Kawabata, K. Miyazono, and T. Taga, Science 284:479-482, 1999). However, the mechanisms that govern astrogliogenesis during the determination of the fate of neural stem cells remain elusive. Here we found that LIF induces expression of BMP2 via STAT3 activation and leads to the consequent activation of Smad1 to efficiently promote astrogliogenic differentiation of NECs. The BMP antagonist Noggin abrogated LIF-induced Smadl activation and astrogliogenesis by inhibiting BMPs produced by NECs. NECs deficient in suppressor of cytokine signaling 3 (SOCS3), a negative regulator of STAT3, readily differentiated into astrocytes upon activation by LIF not only due to sustained activation of STAT3 but also because of the consequent activation of Smadl. Our study suggests a novel LIF-triggered positive regulatory loop that enhances astrogliogenesis.

Original languageEnglish
Pages (from-to)4931-4937
Number of pages7
JournalMolecular and Cellular Biology
Volume27
Issue number13
DOIs
Publication statusPublished - 2007 Jul
Externally publishedYes

Fingerprint

Leukemia Inhibitory Factor
Bone Morphogenetic Proteins
Neural Stem Cells
Neuroepithelial Cells
Astrocytes
Bone Morphogenetic Protein 2
STAT3 Transcription Factor
Brain Injuries
Cytokines

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Potentiation of astrogliogenesis by STAT3-mediated activation of bone morphogenetic protein-Smad signaling in neural stem cells. / Fukuda, Shinji; Abematsu, Masahiko; Mori, Hiroyuki; Yanagisawa, Makoto; Kagawa, Tetsushi; Nakashima, Kinichi; Yoshimura, Akihiko; Taga, Tetsuya.

In: Molecular and Cellular Biology, Vol. 27, No. 13, 07.2007, p. 4931-4937.

Research output: Contribution to journalArticle

Fukuda, Shinji ; Abematsu, Masahiko ; Mori, Hiroyuki ; Yanagisawa, Makoto ; Kagawa, Tetsushi ; Nakashima, Kinichi ; Yoshimura, Akihiko ; Taga, Tetsuya. / Potentiation of astrogliogenesis by STAT3-mediated activation of bone morphogenetic protein-Smad signaling in neural stem cells. In: Molecular and Cellular Biology. 2007 ; Vol. 27, No. 13. pp. 4931-4937.
@article{e836b3bd94bd4d10bcff20fef002b92d,
title = "Potentiation of astrogliogenesis by STAT3-mediated activation of bone morphogenetic protein-Smad signaling in neural stem cells",
abstract = "Astrocytes play important roles in brain development and injury response. Transcription factors STAT3 and Smadl, activated by leukemia inhibitory factor (LIF) and bone morphogenetic protein 2 (BMP2), respectively, form a complex with the coactivator p300 to synergistically induce astrocytes from neuroepithelial cells (NECs) (K. Nakashima, M. Yanagisawa, H. Arakawa, N. Kimura, T. Hisatsune, M. Kawabata, K. Miyazono, and T. Taga, Science 284:479-482, 1999). However, the mechanisms that govern astrogliogenesis during the determination of the fate of neural stem cells remain elusive. Here we found that LIF induces expression of BMP2 via STAT3 activation and leads to the consequent activation of Smad1 to efficiently promote astrogliogenic differentiation of NECs. The BMP antagonist Noggin abrogated LIF-induced Smadl activation and astrogliogenesis by inhibiting BMPs produced by NECs. NECs deficient in suppressor of cytokine signaling 3 (SOCS3), a negative regulator of STAT3, readily differentiated into astrocytes upon activation by LIF not only due to sustained activation of STAT3 but also because of the consequent activation of Smadl. Our study suggests a novel LIF-triggered positive regulatory loop that enhances astrogliogenesis.",
author = "Shinji Fukuda and Masahiko Abematsu and Hiroyuki Mori and Makoto Yanagisawa and Tetsushi Kagawa and Kinichi Nakashima and Akihiko Yoshimura and Tetsuya Taga",
year = "2007",
month = "7",
doi = "10.1128/MCB.02435-06",
language = "English",
volume = "27",
pages = "4931--4937",
journal = "Molecular and Cellular Biology",
issn = "0270-7306",
publisher = "American Society for Microbiology",
number = "13",

}

TY - JOUR

T1 - Potentiation of astrogliogenesis by STAT3-mediated activation of bone morphogenetic protein-Smad signaling in neural stem cells

AU - Fukuda, Shinji

AU - Abematsu, Masahiko

AU - Mori, Hiroyuki

AU - Yanagisawa, Makoto

AU - Kagawa, Tetsushi

AU - Nakashima, Kinichi

AU - Yoshimura, Akihiko

AU - Taga, Tetsuya

PY - 2007/7

Y1 - 2007/7

N2 - Astrocytes play important roles in brain development and injury response. Transcription factors STAT3 and Smadl, activated by leukemia inhibitory factor (LIF) and bone morphogenetic protein 2 (BMP2), respectively, form a complex with the coactivator p300 to synergistically induce astrocytes from neuroepithelial cells (NECs) (K. Nakashima, M. Yanagisawa, H. Arakawa, N. Kimura, T. Hisatsune, M. Kawabata, K. Miyazono, and T. Taga, Science 284:479-482, 1999). However, the mechanisms that govern astrogliogenesis during the determination of the fate of neural stem cells remain elusive. Here we found that LIF induces expression of BMP2 via STAT3 activation and leads to the consequent activation of Smad1 to efficiently promote astrogliogenic differentiation of NECs. The BMP antagonist Noggin abrogated LIF-induced Smadl activation and astrogliogenesis by inhibiting BMPs produced by NECs. NECs deficient in suppressor of cytokine signaling 3 (SOCS3), a negative regulator of STAT3, readily differentiated into astrocytes upon activation by LIF not only due to sustained activation of STAT3 but also because of the consequent activation of Smadl. Our study suggests a novel LIF-triggered positive regulatory loop that enhances astrogliogenesis.

AB - Astrocytes play important roles in brain development and injury response. Transcription factors STAT3 and Smadl, activated by leukemia inhibitory factor (LIF) and bone morphogenetic protein 2 (BMP2), respectively, form a complex with the coactivator p300 to synergistically induce astrocytes from neuroepithelial cells (NECs) (K. Nakashima, M. Yanagisawa, H. Arakawa, N. Kimura, T. Hisatsune, M. Kawabata, K. Miyazono, and T. Taga, Science 284:479-482, 1999). However, the mechanisms that govern astrogliogenesis during the determination of the fate of neural stem cells remain elusive. Here we found that LIF induces expression of BMP2 via STAT3 activation and leads to the consequent activation of Smad1 to efficiently promote astrogliogenic differentiation of NECs. The BMP antagonist Noggin abrogated LIF-induced Smadl activation and astrogliogenesis by inhibiting BMPs produced by NECs. NECs deficient in suppressor of cytokine signaling 3 (SOCS3), a negative regulator of STAT3, readily differentiated into astrocytes upon activation by LIF not only due to sustained activation of STAT3 but also because of the consequent activation of Smadl. Our study suggests a novel LIF-triggered positive regulatory loop that enhances astrogliogenesis.

UR - http://www.scopus.com/inward/record.url?scp=34347338700&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34347338700&partnerID=8YFLogxK

U2 - 10.1128/MCB.02435-06

DO - 10.1128/MCB.02435-06

M3 - Article

VL - 27

SP - 4931

EP - 4937

JO - Molecular and Cellular Biology

JF - Molecular and Cellular Biology

SN - 0270-7306

IS - 13

ER -