Conditional deletion of Stat3 promotes neurogenesis and inhibits astrogliogenesis in neural stem cells

被引：87

作者：

Cao, Fang ^{[1
]}

Hata, Ryuji ^{[1
]}

Zhu, Pengxiang ^{[1
]}

Nakashiro, Koh-ichi ^{[2
]}

Sakanaka, Masahiro ^{[1
]}

机构：

[1] Ehime Univ, Dept Funct Histol, Grad Sch Med, Toon, Ehime 7910295, Japan

[2] Ehime Univ, Dept Oral & Maxillofacial Surg, Grad Sch Med, Toon, Ehime 7910295, Japan

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2010年 / 394卷 / 03期

关键词：

Cre; Notch; Hes; Neural precursor cell; SELF-RENEWAL; NOTCH; EXPRESSION; MAINTENANCE; ACTIVATION; LOOP;

D O I：

10.1016/j.bbrc.2010.03.092

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Although signal transducer and activator of transcription 3 (Stat3) plays crucial roles in the determination of neural stem cell (NSC) fate, Stat3 has multiple roles in NSC function Moreover, Stat3 plays important roles in neuronal survival and tumorigenesis. To investigate the overall effects of Stat3 on NSC fate, NSC were isolated from Stat3(flox/flox) mouse embryos (E14-15d), in which both Stat3 alleles are flanked by LoxP sites Isolated NSC was inoculated with an adenovirus vector expressing Cre recombinase (Ad nCre) or a control adenovirus vector expressing beta-galactosidase (Ad.nLz). Three days later, quantitative real-time PCR (qPCR) analysis revealed that treatment with Ad.nCre eliminated sun 3 mRNA expression in NSC Promoter assay confirmed that overexpression of nCre inhibited transactivation of acute responsive element (APRE) and blocked Stat3 function in NSC Moreover, Western blot analysis and immunocytochemical analysis revealed that elimination of Stat3 in NSC promoted neurogenesis and inhibited astrogliogenesis In addition, we investigated the effects of Stat3 elimination in NSC on the mRNA expression of Notch family members and bHLH factors Consequently, qPCR analysis showed that elimination of Stat3 in NSC promoted neurogenesis and inhibited astrogliogenesis through down-regulation of notch!, notch2 and hes5, but not hes1 mRNA expression (C) 2010 Elsevier Inc All rights reserved

引用

页码：843 / 847

页数：5

共 28 条

[1]

For the long run: Maintaining germinal niches in the adult brain [J].

Alvarez-Buylla, A ;

Lim, DA .

NEURON, 2004, 41 (05) :683-686

[2]

Notch signaling: Cell fate control and signal integration in development [J].

Artavanis-Tsakonas, S ;

Rand, MD ;

Lake, RJ .

SCIENCE, 1999, 284 (5415) :770-776

[3]

Beatus P, 1998, J NEUROSCI RES, V54, P125, DOI 10.1002/(SICI)1097-4547(19981015)54:2<125::AID-JNR1>3.3.CO

[4]

2-C

[5]

Bugga L, 1998, J NEUROBIOL, V36, P509, DOI 10.1002/(SICI)1097-4695(19980915)36:4<509::AID-NEU5>3.0.CO

[6]

2-#

[7]

Overexpression of SOCS3 inhibits astrogliogenesis and promotes maintenance of neural stem cells [J].

Cao, Fang ;

Hata, Ryuji ;

Zhu, Pengxiang ;

Ma, Yong-Jie ;

Tanaka, Junya ;

Hanakawa, Yasushi ;

Hashimoto, Koji ;

Niinobe, Michio ;

Yoshikawa, Kazuaki ;

Sakanaka, Masahiro .

JOURNAL OF NEUROCHEMISTRY, 2006, 98 (02) :459-470

[8]

Chojnacki A, 2003, J NEUROSCI, V23, P1730

[9]

Regulation of neural progenitor cell development in the nervous system [J].

Corbin, Joshua G. ;

Gaiano, Nicholas ;

Juliano, Sharon L. ;

Poluch, Sylvie ;

Stancik, Elizabeth ;

Haydar, Tarik F. .

JOURNAL OF NEUROCHEMISTRY, 2008, 106 (06) :2272-2287

[10]

Suppression of Stat3 promotes neurogenesis in cultured neural stem cells [J].

Gu, F ;

Hata, R ;

Ma, YJ ;

Tanaka, J ;

Mitsuda, N ;

Kumon, Y ;

Hanakawa, Y ;

Hashimoto, K ;

Nakajima, K ;

Sakanaka, M .

JOURNAL OF NEUROSCIENCE RESEARCH, 2005, 81 (02) :163-171

← 1 2 3 →