Down’s syndrome and stem cells
The original article in this thread describes advances in stem cell treatments for Down’s syndrome. Various studies have recognised that there are stem cells defects in Down’s syndrome. For example, a 2006 study from the Stem Cell Research Group in the Royal Manchester Children’s Hospital in the UK found that there was haematopoietic stem cell deficiency and telomere shortening in Down’s syndrome foetuses and bone marrow from children with Down’s syndrome compared to age-matched healthy controls. This was proposed to be a potentially contributory factor in the susceptibility of Down’s syndrome individuals to leukaemia. Thus studying stem cells and considering stem cell therapy in Down’s syndrome is a rational proposition.
More recent studies from Stanford University School of Medicine and published in the highly influential journal Nature, have identified a gene, Usp16, that could be important in reduction of haematopoietic stem cell renewal in Down’s syndrome. Usp16 is a major deubiquitinase for histone H2A. H2A deubiquitination is important in cell cycle progression and gene expression. The study from Stanford used a mouse model of Down’s syndrome termed Ts65Dn. These mice are trisomic for a portion of chromosome 16 with homology to 132 genes on human chromosome 21. The study showed that trisomy of Usp16 resulted in reduced haematopoietic stem cell renewal, as well as reduced expansion of mammary epithelial cells, neural progenitors and fibroblasts and accelerated fibroblast senescence. The study used both mutation of Usp16 or down-regulation by short interfering RNA to examine whether reduction of Usp16 expression has any effect on these defects; it was confirmed that the defects were improved. In confirmatory experiments in human tissues, it was demonstrated that over-expression of Usp16 abrogated fibroblast and neural progenitor expansion while down-regulation of Usp16 in Down’s syndrome fibroblasts rescued their proliferation defects. Thus Usp16 has been identified as a potential therapeutic target, possibly for gene therapy, for some of the pathologies associated with Down’s syndrome.
Sources
ADORNO, M. et al., 2013. Usp16 contributes to somatic stem-cell defects in Down's syndrome. Nature, 501(7467), pp. 380-384
DE VITA, S. et al., 2010. Trisomic dose of several chromosome 21 genes perturbs haematopoietic stem and progenitor cell differentiation in Down's syndrome. England: Nature Publishing Group.
HOLMES, D.K. et al., 2006. Hematopoietic progenitor cell deficiency in fetuses and children affected by Down's syndrome. Experimental hematology, 34(12), pp. 1611-1615
JOO, H. et al., 2007. Regulation of cell cycle progression and gene expression by H2A deubiquitination. Nature, 449(7165), pp. 1068-1072
The original article in this thread describes advances in stem cell treatments for Down’s syndrome. Various studies have recognised that there are stem cells defects in Down’s syndrome. For example, a 2006 study from the Stem Cell Research Group in the Royal Manchester Children’s Hospital in the UK found that there was haematopoietic stem cell deficiency and telomere shortening in Down’s syndrome foetuses and bone marrow from children with Down’s syndrome compared to age-matched healthy controls. This was proposed to be a potentially contributory factor in the susceptibility of Down’s syndrome individuals to leukaemia. Thus studying stem cells and considering stem cell therapy in Down’s syndrome is a rational proposition.
More recent studies from Stanford University School of Medicine and published in the highly influential journal Nature, have identified a gene, Usp16, that could be important in reduction of haematopoietic stem cell renewal in Down’s syndrome. Usp16 is a major deubiquitinase for histone H2A. H2A deubiquitination is important in cell cycle progression and gene expression. The study from Stanford used a mouse model of Down’s syndrome termed Ts65Dn. These mice are trisomic for a portion of chromosome 16 with homology to 132 genes on human chromosome 21. The study showed that trisomy of Usp16 resulted in reduced haematopoietic stem cell renewal, as well as reduced expansion of mammary epithelial cells, neural progenitors and fibroblasts and accelerated fibroblast senescence. The study used both mutation of Usp16 or down-regulation by short interfering RNA to examine whether reduction of Usp16 expression has any effect on these defects; it was confirmed that the defects were improved. In confirmatory experiments in human tissues, it was demonstrated that over-expression of Usp16 abrogated fibroblast and neural progenitor expansion while down-regulation of Usp16 in Down’s syndrome fibroblasts rescued their proliferation defects. Thus Usp16 has been identified as a potential therapeutic target, possibly for gene therapy, for some of the pathologies associated with Down’s syndrome.
Sources
ADORNO, M. et al., 2013. Usp16 contributes to somatic stem-cell defects in Down's syndrome. Nature, 501(7467), pp. 380-384
DE VITA, S. et al., 2010. Trisomic dose of several chromosome 21 genes perturbs haematopoietic stem and progenitor cell differentiation in Down's syndrome. England: Nature Publishing Group.
HOLMES, D.K. et al., 2006. Hematopoietic progenitor cell deficiency in fetuses and children affected by Down's syndrome. Experimental hematology, 34(12), pp. 1611-1615
JOO, H. et al., 2007. Regulation of cell cycle progression and gene expression by H2A deubiquitination. Nature, 449(7165), pp. 1068-1072
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