Culture in reduced levels of oxygen promotes clonogenic sympathoadrenal differentiation by isolated neural crest stem cells

S. J. Morrison, M. Csete, A. K. Groves, W. Melega, B. Wold, D. J. Anderson

Research output: Contribution to journalArticle

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Abstract

Isolated neural crest stem cells (NCSCs) differentiate to autonomic neurons in response to bone morphogenetic protein 2 (BMP2) in clonal cultures, but these neurons do not express sympathoadrenal (SA) lineage markers. Whether this reflects a developmental restriction in NCSCs or simply inappropriate culture conditions was not clear. We tested the growth and differentiation potent a of NCSCs at ~5% O2, which more closely approximates physiological oxygen levels. Eighty-three percent of p75+P0 - cells isolated from embryonic day 14.5 sciatic nerve behaved as stem cells under these conditions, suggesting that this is a nearly pure population. Furthermore, addition of BMP2 plus forskolin in decreased oxygen cultures elicited differentiation of thousands of cells expressing tyrosine hydroxylase, dopamine-β-hydroxylase, and the SA lineage marker SA-1 in nearly all colonies. Such cells also synthesized and released dopamine and norepinephrine. These data demonstrate that isolated mammalian NCSCs uniformly possess SA lineage capacity and further suggest that oxygen levels can influence cell fate. Parallel results indicating that reduced oxygen levels can also promote the survival, proliferation, and catecholaminergic differentiation of CNS stem cells (Studer et al., 2000) suggests that neural stem cells may exhibit a conserved response to reduced oxygen levels.

Original languageEnglish (US)
Pages (from-to)7370-7376
Number of pages7
JournalJournal of Neuroscience
Volume20
Issue number19
StatePublished - Oct 1 2000

Fingerprint

Neural Stem Cells
Neural Crest
Oxygen
Bone Morphogenetic Protein 2
Dopamine
Stem Cells
Neurons
Tyrosine 3-Monooxygenase
Sciatic Nerve
Colforsin
Mixed Function Oxygenases
Cell Differentiation
Norepinephrine
Growth
Population

Keywords

  • Autonomic differentiation
  • Cell fate determination
  • Dopamine
  • Hypoxia
  • Neural crest
  • Noradrenergic
  • Oxygen
  • Stem cell
  • Sympathetic neuron
  • Sympathoadrenal

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Culture in reduced levels of oxygen promotes clonogenic sympathoadrenal differentiation by isolated neural crest stem cells. / Morrison, S. J.; Csete, M.; Groves, A. K.; Melega, W.; Wold, B.; Anderson, D. J.

In: Journal of Neuroscience, Vol. 20, No. 19, 01.10.2000, p. 7370-7376.

Research output: Contribution to journalArticle

Morrison, S. J. ; Csete, M. ; Groves, A. K. ; Melega, W. ; Wold, B. ; Anderson, D. J. / Culture in reduced levels of oxygen promotes clonogenic sympathoadrenal differentiation by isolated neural crest stem cells. In: Journal of Neuroscience. 2000 ; Vol. 20, No. 19. pp. 7370-7376.
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