Directing neurotransmitter identity of neurones derived from expanded adult neural stem cells.
In-vitro expanded neural stem cells (NSCs) of the adult subependymal zone (SEZ) may serve as a source for replacing degenerating neurones in disease and trauma. Crucial for the viability of this approach is the ability to selectively generate specific types of neurones from these cells. Here we show that NSCs derived from the adult mouse SEZ and expanded in vitro as neurosphere cells lose their in-vivo specification and generate a mixture of progeny comprising both GABAergic and also, surprisingly, glutamatergic neurones. When forced to express the pro-neural transcription factor neurogenin 2, virtually all progeny of in-vitro expanded adult NSCs acquire a glutamatergic identity, whereas only GABAergic neurones are generated upon expression of the transcription factor Mash1. Respecification of expanded NSCs from the adult SEZ by neurogenin 2 was accompanied by upregulation of the T-box transcription factor Tbr1, suggesting that their progeny had acquired a dorsal telencephalic identity. Thus, in-vitro expanded adult NSCs have the competence to become directed towards distinct functional neurotransmitter phenotypes when the appropriate transcriptional cues are provided.
Berninger
Benedikt
B
Department of Physiological Genomics, Institute of Physiology, Ludwig-Maximilians University Munich, Munich, Germany. benedikt.berninger@gsf.de
Guillemot
François
F
Götz
Magdalena
M
D053687:Adult Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D018929:Cell Culture Techniques / Q000379:methods; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics*; D019070:Cell Lineage / Q000187:drug effects / Q000235:genetics*; D002469:Cell Separation / Q000379:methods; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000235:genetics; D018698:Glutamic Acid / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000378:metabolism / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010641:Phenotype; D018874:Spheroids, Cellular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D020825:T-Box Domain Proteins; D013687:Telencephalon / Q000166:cytology / Q000196:embryology*; D015533:Transcriptional Activation / Q000187:drug effects / Q000235:genetics; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D018698:Glutamic Acid; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D020825:T-Box Domain Proteins; D005680:gamma-Aminobutyric Acid; C499317:Ascl1 protein, mouse; C102938:Neurog2 protein, mouse; C492271:Tbr1 protein, mouse