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- Title
Gene expression in human neural stem cells: effects of leukemia inhibitory factor.
- Authors
Wright, Lynda S.; Li, Jiang; Caldwell, Maeve A.; Wallace, Kyle; Johnson, Jeffrey A.; Svendsen, Clive N.
- Abstract
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 (ltNSC[sup ctx]) for up to 110 population doublings. We established basal gene expression in ltNSC[sup ctx] 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 ltNSC[sup ctx] cultures capable of long-term self renewal, and reveals specific sets of genes that are directly or indirectly regulated by LIF.
- Subjects
EPIDERMAL growth factor; LEUKEMIA inhibitory factor; STEM cells
- Publication
Journal of Neurochemistry, 2003, Vol 86, Issue 1, p179
- ISSN
0022-3042
- Publication type
Article
- DOI
10.1046/j.1471-4159.2003.01826.x