title: Stem and progenitor cell dysfunction in human trisomies.
abstract: Trisomy 21, the commonest constitutional aneuploidy in humans, causes profound perturbation of stem and progenitor cell growth, which is both cell context dependent and developmental stage specific and mediated by complex genetic mechanisms beyond increased Hsa21 gene dosage. While proliferation of fetal hematopoietic and testicular stem/progenitors is increased and may underlie increased susceptibility to childhood leukemia and testicular cancer, fetal stem/progenitor proliferation in other tissues is markedly impaired leading to the characteristic craniofacial, neurocognitive and cardiac features in individuals with Down syndrome. After birth, trisomy 21-mediated premature aging of stem/progenitor cells may contribute to the progressive multi-system deterioration, including development of Alzheimer's disease.
authors.affiliation: Department of Paediatrics and Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Oxford, UK.
authors.forename: Binbin
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Statistics, University of Oxford, Oxford, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Filippi
authors.affiliation: Centre for Haematology, Imperial College London, London, UK.
authors.forename: Anindita
authors.initials: A
authors.lastname: Roy
authors.affiliation: Department of Paediatrics and Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Oxford, UK irene.roberts@paediatrics.ox.ac.uk.
authors.forename: Irene
authors.initials: I
authors.lastname: Roberts
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004314:Down Syndrome / Q000209:etiology* / Q000235:genetics / Q000473:pathology*; D006410:Hematopoiesis / Q000235:genetics; D006801:Humans; D057026:Induced Pluripotent Stem Cells; D010641:Phenotype; D013234:Stem Cells / Q000473:pathology* / Q000502:physiology; D014314:Trisomy / Q000473:pathology*
keywords: Down syndrome; hematopoietic stem cells; leukemia; neural progenitors; trisomy 21