Expression of signal transducers and activator of transcription 3 (STAT3) determines differentiation of olfactory bulb cells.
Signal transducers and activator of transcription (STAT) proteins are activated in response to many cytokines and growth factors. Many studies indicated that regulation of STAT expression plays an important role in survival, growth, and differentiation of neurons and glias in response to ciliary neurotropic factor, including rehabilitation of rat cortical injury, nerve regeneration, gangliosides-mediated stimulation of rat and murine primary microglia, and differentiation of retinal neurons. In this study, we use olfactory bulb neurons as a useful model, which undergo strong neurogenesis throughout adulthood. Our research demonstrated that low level of STAT3 expression facilitates the terminal differentiation of olfactory bulb neurons as well as induces the generation of neurons from neural stem cells, which can be potentially used in future therapies. On the contrary, activation of STAT3 expression is essential to the maintenance of stem-like status in olfactory cells. This activation can be manipulated by leukemia inhibitory factor (LIF), a member of cytosolic tyrosine kinases. All these results implicate that STAT3 serves as a critical protein in regulating the differentiation state in neural cells.
Yu
Yiqun
Y
Research and Development Department, Jianrong Biochemistry and Nanomaterial Limited Corporation, 7 Qingnian Road, Industrial Development Zone of Eastern Juancheng County 274600, Shandong Province, China.
Ren
Wenwen
W
Ren
Baozhong
B
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D004815:Epidermal Growth Factor / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006801:Humans; D007381:Intermediate Filament Proteins / Q000378:metabolism; D053605:Leukemia Inhibitory Factor / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009830:Olfactory Bulb / Q000166:cytology / Q000502:physiology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
D007381:Intermediate Filament Proteins; D053605:Leukemia Inhibitory Factor; C577484:NES protein, human; D009419:Nerve Tissue Proteins; C577486:Nes protein, rat; D064231:Nestin; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; D016222:Fibroblast Growth Factor 2; D004815:Epidermal Growth Factor
Science. 1997 Apr 4;276(5309):66-71
9082987
Nature. 2002 Jul 4;418(6893):50-6
12077607
Development. 1994 Dec;120(12):3519-28
7821219
J Immunol. 1999 Apr 15;162(8):4637-46
10202003
Science. 1999 Oct 15;286(5439):548-52
10521353
Dev Biol. 1980 Jan;74(1):205-15
7350009
Brain Res Dev Brain Res. 2004 Jul 19;151(1-2):159-68
15246702
Development. 1993 Mar;117(3):1173-82
8325241
Cell. 1992 Jan 10;68(1):33-51
1732063
J Neurosci. 2005 Feb 16;25(7):1645-53
15716400
Curr Opin Cell Biol. 2004 Dec;16(6):713-20
15530786
Curr Opin Cell Biol. 2001 Apr;13(2):211-7
11248555
Stem Cells. 2004;22(5):798-811
15342944
Proc Natl Acad Sci U S A. 2004 Mar 30;101(13):4661-6
15070774
Nature. 1995 Mar 23;374(6520):367-70
7885477
J Theor Biol. 2005 Oct 7;236(3):311-22
15950988
J Neurosci. 2004 May 5;24(18):4432-43
15128857
Prog Neurobiol. 2000 Dec;62(5):527-59
10869782
J Biol Chem. 1996 May 31;271(22):13023-32
8662645
Prog Neurobiol. 1997 Aug;52(5):355-78
9304697
J Neurosci. 2001 Sep 15;21(18):7161-70
11549727
Trends Neurosci. 1996 Mar;19(3):102-9
9054056
Genes Dev. 1996 Dec 15;10(24):3129-40
8985182
J Neurosci. 1999 Feb 1;19(3):1049-61
9920668
J Neurobiol. 1995 Sep;28(1):35-50
8586964
J Immunol. 2004 Sep 15;173(6):3844-54
15356132
Nat Med. 1998 Nov;4(11):1313-7
9809557
Science. 2000 Feb 25;287(5457):1433-8
10688783
J Cell Biol. 2002 Jan 21;156(2):287-97
11807093
EMBO J. 1987 Dec 20;6(13):3995-4002
3127201
Int J Dev Neurosci. 2000 Jul-Aug;18(4-5):439-46
10817928
J Neurosci. 2004 Nov 3;24(44):9779-88
15525763
J Neurosci. 1991 May;11(5):1243-55
1851216
Annu Rev Neurosci. 2005;28:57-87
16022590
Genomics. 1994 Apr;20(3):452-62
8034318
Stem Cells. 1999;17(3):127-37
10342555
Anat Rec. 1999 Aug 15;257(4):137-48
10467245
Annu Rev Neurosci. 2001;24:677-736
11520916
Cell. 1999 Jun 11;97(6):703-16
10380923
Annu Rev Neurosci. 1995;18:159-92
7605059
Neuroscience. 2001;106(3):589-601
11591459
J Neurosci. 2003 Jan 1;23(1):240-51
12514221
Stem Cells. 2004;22(3):396-404
15153616