Stem and progenitor cell dysfunction in human trisomies |
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| Authors: | Binbin Liu Sarah Filippi Anindita Roy Irene Roberts |
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| Affiliation: | 1. Department of Paediatrics and Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Oxford, UK;2. Department of Statistics, University of Oxford, Oxford, UK;3. Centre for Haematology, Imperial College London, London, UK |
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| 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. |
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| Keywords: | Down syndrome hematopoietic stem cells leukemia neural progenitors trisomy 21 |
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