title: Neural precursor cells from a fatal human motoneuron disease differentiate despite aberrant gene expression.
abstract: Precursor cells of the human central nervous system can be cultured in vitro to reveal pathogenesis of diseases or developmental disorders. Here, we have studied the biology of neural precursor cells (NPCs) from patients of lethal congenital contracture syndrome (LCCS), a severe motoneuron disease leading to prenatal death before the 32nd gestational week. LCCS fetuses are immobile because of a motoneuron defect, seen as degeneration of the anterior horn and descending tracts of the developing spinal cord. The genetic defect for the syndrome is unknown. We show that NPCs isolated postmortem from LCCS fetuses grow and are maintained in culture, but display increased cell cycle activity. Global transcript analysis of undifferentiated LCCS precursor cells present with changes in EGF-related signaling when compared with healthy age-matched human controls. Further, we show that LCCS-derived NPCs differentiate into cells of neuronal and glial lineage and that the initial differentiation is not accompanied by overt apoptosis. Cells expressing markers Islet-1 and Hb9 are also generated from the LCCS NPCs, suggesting that the pathogenic mechanism of LCCS does not directly affect the differentiation capacity or survival of the cells, but the absence of motoneurons in LCCS may be caused by a noncell autonomous mechanism.
authors: Department of Molecular Medicine, National Public Health Institute, Biomedicum, Helsinki, Finland.
authors: Niklas
authors: N
authors: Pakkasjärvi
authors: Laura
authors: L
authors: Kerosuo
authors: Heidi
authors: H
authors: Nousiainen
authors: Massimiliano
authors: M
authors: Gentile
authors: Juha
authors: J
authors: Saharinen
authors: Satu
authors: S
authors: Suhonen
authors: Hannu
authors: H
authors: Sariola
authors: Leena
authors: L
authors: Peltonen
authors: Marjo
authors: M
authors: Kestilä
authors: Kirmo
authors: K
authors: Wartiovaara
mesh_terms: D017209:Apoptosis; D001973:Bromodeoxyuridine / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D005333:Fetus / Q000473:pathology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006801:Humans; D046228:Microarray Analysis / Q000379:methods; D016472:Motor Neuron Disease / Q000473:pathology*; D009474:Neurons / Q000166:cytology*; D013234:Stem Cells / Q000473:pathology / Q000502:physiology*
chemical_list: D001973:Bromodeoxyuridine