Fibroblast growth factor induces a neural stem cell phenotype in foetal forebrain progenitors and during embryonic stem cell differentiation.
Neural stem (NS) cell lines may be derived via differentiation of pluripotent embryonic stem (ES) cells or from foetal forebrain. However, because NS cells arise in vitro from heterogeneous populations their immediate cellular origin remains unclear. We used microarray-based expression profiling to identify a set of markers expressed by mouse NS cells but not ES cells. One differentially expressed gene encodes the cell surface protein, CD44. CD44 expression is activated by FGF-2 in a subset of cells in both differentiating ES cells and foetal forebrain cultures. Following isolation by flow cytometry the CD44+ population was found to be highly enriched for NS cell founders. We found that other NS cell marker genes are also induced by FGF in culture, including: Adam12, Cadherin20, Cx3cl1, EGFR, Frizzled9, Kitl, Olig1, Olig2 and Vav3. We speculate that the self-renewing NS cell state may be generated in vitro following transcriptional resetting induced by FGF.
Pollard
Steven M
SM
Wellcome Trust Centre for Stem Cell Research, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QR, UK. smp54@cam.ac.uk
Wallbank
Richard
R
Tomlinson
Simon
S
Grotewold
Lars
L
Smith
Austin
A
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D005260:Female; D005346:Fibroblast Growth Factors / Q000494:pharmacology*; D005819:Genetic Markers / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D010641:Phenotype; D011247:Pregnancy; D016548:Prosencephalon / Q000166:cytology* / Q000187:drug effects / Q000502:physiology
D005819:Genetic Markers; D005346:Fibroblast Growth Factors