Gene expression in human neural stem cells: Effects of leukemia inhibitory factor

Lynda S. Wright, Jiang Li, Maeve A. Caldwell, Kyle Wallace, Jeffrey A. Johnson, Clive N. Svendsen*

*Corresponding author for this work

Research output: Contribution to journalArticle

142 Scopus citations

Abstract

Human neural precursor cells grown in culture provide a source of tissue for drug screening, developmental studies and cell therapy. However, mechanisms underlying their growth and differentiation are poorly understood. We show that epidermal growth factor (EGF) responsive precursors derived from the developing human cortex undergo senescence after 30-40 population doublings. Leukemia inhibitory factor (LIF) increased overall expansion rates, prevented senescence and allowed the growth of a long-term self renewing neural stem cell (ItNSCctx) for up to 110 population doublings. We established basal gene expression in ItNSCctx using Affymetrix oligonucleotide microarrays that delineated specific members of important growth factor and signaling families consistently expressed across three separate lines. Following LIF withdrawal, 200 genes showed significant decreases. Protein analysis confirmed LIF-regulated expression of glial fibrillary acidic protein, CD44, and major histocompatibility complex I. This study provides the first molecular profile of human ItNSCctx cultures capable of long-term self renewal, and reveals specific sets of genes that are directly or indirectly regulated by LIF.

Original languageEnglish (US)
Pages (from-to)179-195
Number of pages17
JournalJournal of neurochemistry
Volume86
Issue number1
DOIs
StatePublished - Jul 1 2003

Keywords

  • Epidermal growth factor
  • Leukemia inhibitory factor
  • Microarray
  • Neural stem cells
  • Neurosphere

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'Gene expression in human neural stem cells: Effects of leukemia inhibitory factor'. Together they form a unique fingerprint.

  • Cite this

    Wright, L. S., Li, J., Caldwell, M. A., Wallace, K., Johnson, J. A., & Svendsen, C. N. (2003). Gene expression in human neural stem cells: Effects of leukemia inhibitory factor. Journal of neurochemistry, 86(1), 179-195. https://doi.org/10.1046/j.1471-4159.2003.01826.x