Gene expression in human neural stem cells: effects of leukemia inhibitory factor.
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 (ltNSCctx) for up to 110 population doublings. We established basal gene expression in ltNSCctx 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 ltNSCctx cultures capable of long-term self renewal, and reveals specific sets of genes that are directly or indirectly regulated by LIF.
Wright
Lynda S
LS
The Waisman Center Stem Cell Research Program and Department of Anatomy, University of Wisconsin, 53705, USA.
Li
Jiang
J
Caldwell
Maeve A
MA
Wallace
Kyle
K
Johnson
Jeffrey A
JA
Svendsen
Clive N
CN
D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D006131:Growth Inhibitors / Q000494:pharmacology*; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013995:Time
D005904:Glial Fibrillary Acidic Protein; D006131:Growth Inhibitors; D015395:Histocompatibility Antigens Class I; D018960:Hyaluronan Receptors; D015850:Interleukin-6; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines; D004815:Epidermal Growth Factor