Potency and fate specification in CNS stem cell populations in vitro.
To realize the promise of stem cell biology, it is important to identify the precise time in the history of the cell when developmental potential is restricted. To achieve this goal, we developed a real-time imaging system that captures the transitions in fate, generating neurons, astrocytes, and oligodendrocytes from single CNS stem cells in vitro. In the presence of bFGF, tripotent cells normally produce specified progenitors through a bipotent intermediate cell type. Surprisingly, the tripotent state is reset at each passage. The cytokine CNTF is thought to instruct multipotent cells to an astrocytic fate. We demonstrate that CNTF both directs astrogliogenesis from tripotent cells, bypassing two of the three normal bipotent intermediates, and later promotes the expansion of specified astrocytic progenitors. These results show how discrete cell types emerge from a multipotent cell and provide a strong basis for future studies to determine the molecular basis of fate specification.
Ravin
Rea
R
Laboratory of Molecular Biology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
Hoeppner
Daniel J
DJ
Munno
David M
DM
Carmel
Liran
L
Sullivan
Jim
J
Levitt
David L
DL
Miller
Jennifer L
JL
Athaide
Christopher
C
Panchision
David M
DM
McKay
Ronald D G
RD
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage / Q000502:physiology*; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002490:Central Nervous System / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D020934:Ciliary Neurotrophic Factor / Q000378:metabolism / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism / Q000494:pharmacology; D017930:Genes, Reporter / Q000235:genetics; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics; D019044:Image Cytometry / Q000379:methods; D018715:Microscopy, Video / Q000379:methods; D039902:Multipotent Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D046509:Tissue Culture Techniques / Q000379:methods; D014162:Transfection / Q000379:methods
D020934:Ciliary Neurotrophic Factor; D005904:Glial Fibrillary Acidic Protein; D016222:Fibroblast Growth Factor 2