EGF converts transit-amplifying neurogenic precursors in the adult brain into multipotent stem cells.
Neural stem cells in the subventricular zone (SVZ) continue to generate new neurons in the adult brain. SVZ cells exposed to EGF in culture grow to form neurospheres that are multipotent and self-renewing. We show here that the majority of these EGF-responsive cells are not derived from relatively quiescent stem cells in vivo, but from the highly mitotic, Dlx2(+), transit-amplifying C cells. When exposed to EGF, C cells downregulate Dlx2, arrest neuronal production, and become highly proliferative and invasive. Killing Dlx2(+) cells dramatically reduces the in vivo response to EGF and neurosphere formation in vitro. Furthermore, purified C cells are 53-fold enriched for neurosphere generation. We conclude that transit-amplifying cells retain stem cell competence under the influence of growth factors.
Doetsch
Fiona
F
Department of Molecular and Cellular Biology, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138, USA. doetsch@fas.harvard.edu
Petreanu
Leopoldo
L
Caille
Isabelle
I
Garcia-Verdugo
Jose Manuel
JM
Alvarez-Buylla
Arturo
A
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D001921:Brain / Q000254:growth & development* / Q000378:metabolism* / Q000648:ultrastructure; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology*; D019070:Cell Lineage / Q000187:drug effects / Q000235:genetics; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004815:Epidermal Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D010641:Phenotype; D018874:Spheroids, Cellular / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D014157:Transcription Factors; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
C088334:Distal-less homeobox proteins; D018398:Homeodomain Proteins; D014157:Transcription Factors; D004815:Epidermal Growth Factor; D066246:ErbB Receptors