Single factors direct the differentiation of stem cells from the fetal and adult central nervous system.

Abstract

Identifying the signals that regulate stem cell differentiation is fundamental to understanding cellular diversity in the brain. In this paper we identify factors that act in an instructive fashion to direct the differentiation of multipotential stem cells derived from the embryonic central nervous system (CNS). CNS stem cell clones differentiate to multiple fates: neurons, astrocytes, and oligodendrocytes. The differentiation of cells in a clone is influenced by extracellular signals: Platelet-derived growth factor (PDGF-AA, -AB, and -BB) supports neuronal differentiation. In contrast, ciliary neurotrophic factor and thyroid hormone T3 act instructively on stem cells to generate clones of astrocytes and oligodendrocytes, respectively. Adult stem cells had remarkably similar responses to these growth factors. These results support a simple model in which transient exposure to extrinsic factors acting through known pathways initiates fate decisions by muhipotential CNS stem cells.

Human primitive neuroectodermal tumour cells behave as multipotent neural precursors in response to FGF2

“…A previous study reported that CNTF or T3 increases the proportions of neural stem cells expressing glial phenotypes (Johe et al, 1996) therefore in some experiments T3 (3 ± 15 ng/ml) or CNTF (5 ± 15 ng/ml) were added to cultures of¯oating clusters in the presence of FGF2 2 days before they were plated on polysine and for the next 7 days after plating (as described Johe et al, 1996). Immunocytochemical analysis showed no e ect of treatment with T3 or CNTF on the proportions of cells expressing the di erent neural phenotypes as compared with parallel cultures treated only with FGF2 (data not shown).…”

“…Previous studies in vitro have shown that FGF2 can act as a mitogen for central nervous system stem cells (Johe et al, 1996) and pluripotent progenitor cells from embryonic brain (Gritti et al, 1996;Bartlett, 1993, 1995;Qian et al, 1997). In the de®ned medium Dev cells proliferate exponentially with a (7) stained by an anti-MAP kinase antiserum that recognizes both phosphorylated and non-phosphorylated forms of ERK1 and ERK2.…”

“…CNS stem cells proliferating in response to FGF2 may be either substrate adherent (Johe et al, 1996) or may detach from the substrate to form nonadherent clusters and tightly packed spheres of proliferating cells (Gritti et al, 1996). In the absence of serum, Dev cells adhere to cell culture plastic and grow as clusters of round or fusiform cells, some of which grow short ®ne processes.…”

“…Basic ®broblast growth factor (FGF2) stimulates the proliferation and di erentiation of multipotent CNS stem cells by as yet unidenti®ed mechanisms (Johe et al, 1996;Vescovi et al, 1993;Gritti et al, 1996;Qian et al, 1997) and is present in FCS. FGF receptors (FGFR) have been identi®ed in undi erentiated neuroepithelial cells in vivo and in vitro (Peters et al, 1993;Miyake et al, 1995) and in PNET (Weiner et al, 1996).…”

Ionizing radiation induces apoptosis and inhibits neuronal differentiation in rat neural stem cells via the c-Jun NH2-terminal kinase (JNK) pathway

“…Cell culture for NSCs was performed as described previously (Johe et al, 1996;Erlandsson et al, 2001). Briefly, embryonic neural tissue samples were dissected from the frontal cortex of Fisher 344 rats on gestation day 16 (E16).…”