Selective introduction of antisense oligonucleotides into single adult CNS progenitor cells using electroporation demonstrates the requirement of STAT3 activation for CNTF-induced gliogenesis

• We have developed a novel method in which antisense DNA is selectively electroporated into individual adult neural progenitor cells. By electroporation of antisense oligonucleotides against signal transducer and activator of transcription 3 (STAT3) we demonstrate that ciliary neurotrophic factor (CNTF) is an instructive signal for astroglial type 2 cell fate specifically mediated via activation of STAT3. Activation of the mitogen-activated protein kinase (MAPK) signaling pathway induced only a transient increase in glial fibrillary acidic protein (GFAP) expression, and inhibition of this signaling pathway did not block the induction by CNTF of glial differentiation in progenitor cells. In addition we show that microelectroporation is a new powerful method for introducing antisense agents into single cells in complex cellular networks.

Nyckelord

Age Factors

Animals

Astrocytes/*cytology/enzymology

Cell Differentiation/drug effects/physiology

Cell Division/drug effects/physiology

Cells

Cultured

Ciliary Neurotrophic Factor/*pharmacology

DNA-Binding Proteins/*genetics/metabolism

Electroporation

Enzyme Inhibitors/pharmacology

Flavonoids/pharmacology

Gene Expression/physiology

Genistein/pharmacology

Glial Fibrillary Acidic Protein/metabolism

Hippocampus/*cytology

MAP Kinase Signaling System/physiology

Oligonucleotides

Antisense/*pharmacology

Protein-Tyrosine Kinase/metabolism

Rats

Stem Cells/cytology/*enzymology

Support

Non-U.S. Gov't

Trans-Activators/*genetics/metabolism

Transfection

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)