Directed differentiation of hippocampal stem/progenitor cells in the adult brain.
Adult neurogenesis is a lifelong feature of brain plasticity; however, the potency of adult neural stem/progenitor cells in vivo remains unclear. We found that retrovirus-mediated overexpression of a single gene, the bHLH transcription factor Ascl1, redirected the fate of the proliferating adult hippocampal stem/progenitor (AHP) progeny and lead to the exclusive generation of cells of the oligodendrocytic lineage at the expense of newborn neurons, demonstrating that AHPs in the adult mouse brain are not irrevocably specified in vivo. These data indicate that AHPs have substantial plasticity, which might have important implications for the potential use of endogenous AHPs in neurological disease.
Jessberger
Sebastian
S
Laboratory of Genetics, The Salk Institute for Biological Studies, 10010 N. Torrey Pines Road, La Jolla, California 92037, USA. jessberger@cell.biol.ethz.ch
Toni
Nicolas
N
Clemenson
Gregory D
GD
Ray
Jasodhara
J
Gage
Fred H
FH
D000818:Animals; D000943:Antigens, Differentiation / Q000096:biosynthesis; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000502:physiology*; D001921:Brain / Q000166:cytology*; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D019070:Cell Lineage; D002470:Cell Survival / Q000235:genetics; D002478:Cells, Cultured; D018891:Dentate Gyrus / Q000166:cytology; D005260:Female; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D006624:Hippocampus / Q000166:cytology*; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics; D020547:Lateral Ventricles / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D008979:Moloney murine leukemia virus / Q000235:genetics; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000821:virology; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism / Q000821:virology; D051381:Rats; D013045:Species Specificity; D013234:Stem Cells / Q000166:cytology / Q000502:physiology* / Q000821:virology; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics
D000943:Antigens, Differentiation; D051792:Basic Helix-Loop-Helix Proteins; D049452:Green Fluorescent Proteins; D018398:Homeodomain Proteins; D014157:Transcription Factors; C499317:Ascl1 protein, mouse; C088334:Distal-less homeobox proteins