Astrocytes promote neurogenesis from oligodendrocyte precursor cells.
The oligodendrocyte precursor cell (OPC) has until recently been regarded as a lineage-restricted precursor cell. Considerable interest has been generated by reports suggesting that OPCs may possess a wider differentiation potential than previously assumed and thus be considered a multipotential stem cell. This study examined the neuronal differentiation potential of rat, postnatal cortical OPCs in response to extracellular cues in vitro and in vivo. OPCs did not exhibit intrinsic neuronal potential and were restricted to oligodendrocyte lineage potential following treatment with the neural precursor mitogen fibroblast growth factor 2. In contrast, a postnatal hippocampal astrocyte-derived signal(s) is sufficient to induce functional neuronal differentiation of cortical OPCs in vitro in population and single cell studies. Co-treatment with Noggin, a bone morphogenetic protein antagonist, did not attenuate neuronal differentiation. Following transplantation to the adult rat hippocampus, cortical OPCs expressed doublecortin, a neuroblast-associated marker. The present findings show that hippocampal, astrocyte-derived signals can induce the neuronal differentiation of OPCs through a Noggin-independent mechanism.
Gaughwin
P M
PM
Department of Clinical Neurosciences and Centre for Brain Repair, Forvie Site, Robinson Way, Cambridge CB2 2PY, UK.
Caldwell
M A
MA
Anderson
J M
JM
Schwiening
C J
CJ
Fawcett
J W
JW
Compston
D A S
DA
Chandran
S
S
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000166:cytology*; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002470:Cell Survival; D017690:Cell Transplantation / Q000379:methods; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D018920:Coculture Techniques / Q000379:methods; D017077:Culture Media, Conditioned / Q000494:pharmacology; D003952:Diagnostic Imaging / Q000379:methods; D000089662:Doublecortin Protein; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005434:Flow Cytometry / Q000379:methods; D005732:Gangliosides / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000502:physiology / Q000637:transplantation; D007150:Immunohistochemistry / Q000379:methods; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000502:physiology*; D009836:Oligodendroglia / Q000187:drug effects / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013234:Stem Cells / Q000166:cytology*; D013997:Time Factors; D014162:Transfection / Q000379:methods; D000099176:Noggin Protein
D002118:Calcium; D002352:Carrier Proteins; D017077:Culture Media, Conditioned; D000089662:Doublecortin Protein; D016222:Fibroblast Growth Factor 2; D005732:Gangliosides; D049452:Green Fluorescent Proteins; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D000099176:Noggin Protein; C000714848:Dcx protein, rat; C489787:MAP2 protein, rat; C062875:ganglioside A2B5