Multipotency of FBD-103a, a neural progenitor cell line from the p53-deficient mouse

Makoto Horiuchi, Takayuki Ito, David E Pleasure, Yasuhiro Tomooka

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

We previously established cell lines from brains of p53-deficient embryos, and have now characterized one of these lines, FBD-103a, in detail. Recloning FBD-103a yielded 3 types of subclones: 5 generated the neuronal lineage (Type 1), 3 generated the glial lineage (Type 2), and 10 gave rise to both lineages as the parental line (Type 3), indicating that FBD-103a is a multipotent neural progenitor cell line indistinguishable from true neural stem cells. RT-PCR analyses of transcription factor expression indicated that the transition of multipotent Type 3 clones to either neuronally or glially differentiated progeny was marked by down-regulation of Ascl1/Mash1 and Olig1 and up-regulation of Nrsf/Rest. As expected for neural stem cells, FBD-103a and Type 3 clones formed neurospheres when cultured on a non-adhesive substrate in a serum-free medium containing fibroblast growth factor-2 (FGF2). Interestingly, the transition between Type 3 and Type 1 neuronal- or Type 2 glial-specified cells proved to be reversible; Type 1 and Type 2 subclones could also form neurospheres, from which both neuron-generating and glia-generating progenies could be derived. Moreover, when maintained on an adherent substratum that prevented neurosphere formation, but with FGF2 and without serum, Type 2 clones could generate Type 3 multipotent cells. Thus, at least in the absence of p53, specialized cell-cell interactions within neurospheres are not essential for persistence or recapture of the capacity for self-renewal and multipotency by cells differentiating along glial pathways, a result of possible significance to the pathogenesis of malignant brain tumors.

Original languageEnglish (US)
Pages (from-to)24-36
Number of pages13
JournalBrain Research
Volume1066
Issue number1-2
DOIs
StatePublished - Dec 20 2005
Externally publishedYes

Keywords

  • Clonal cell line
  • Epidermal growth factor
  • Fibroblast growth factor
  • Neurosphere
  • p53 deficiency

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Developmental Biology
  • Molecular Biology

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