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  • 1
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    Statin treatment rescues FGFR3 skeletal dysplasia phenotypes (2014)
    Nature Publishing Group (NPG)
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    Publication Date: 2014-09-19
    Description: Gain-of-function mutations in the fibroblast growth factor receptor 3 gene (FGFR3) result in skeletal dysplasias, such as thanatophoric dysplasia and achondroplasia (ACH). The lack of disease models using human cells has hampered the identification of a clinically effective treatment for these diseases. Here we show that statin treatment can rescue patient-specific induced pluripotent stem cell (iPSC) models and a mouse model of FGFR3 skeletal dysplasia. We converted fibroblasts from thanatophoric dysplasia type I (TD1) and ACH patients into iPSCs. The chondrogenic differentiation of TD1 iPSCs and ACH iPSCs resulted in the formation of degraded cartilage. We found that statins could correct the degraded cartilage in both chondrogenically differentiated TD1 and ACH iPSCs. Treatment of ACH model mice with statin led to a significant recovery of bone growth. These results suggest that statins could represent a medical treatment for infants and children with TD1 and ACH.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yamashita, Akihiro -- Morioka, Miho -- Kishi, Hiromi -- Kimura, Takeshi -- Yahara, Yasuhito -- Okada, Minoru -- Fujita, Kaori -- Sawai, Hideaki -- Ikegawa, Shiro -- Tsumaki, Noriyuki -- England -- Nature. 2014 Sep 25;513(7519):507-11. doi: 10.1038/nature13775. Epub 2014 Sep 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cell Induction and Regulation Field, Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, Kyoto 606-8507, Japan. ; 1] Cell Induction and Regulation Field, Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, Kyoto 606-8507, Japan [2] Department of Pediatrics, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan. ; Department of Obstetrics and Gynecology, Hyogo College of Medicine, Hyogo 663-8501, Japan. ; Laboratory of Bone and Joint Diseases, Center for Integrated Medical Sciences, RIKEN, Tokyo 108-8639, Japan. ; 1] Cell Induction and Regulation Field, Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, Kyoto 606-8507, Japan [2] Japan Science and Technology Agency, CREST, Tokyo 102-0075, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25231866" target="_blank"〉PubMed〈/a〉
    Keywords: Achondroplasia/*drug therapy/genetics/*pathology ; Animals ; Bone Development/drug effects ; Cartilage/cytology/drug effects/pathology ; Cell Differentiation ; Chondrocytes/cytology/pathology ; Disease Models, Animal ; Female ; Fluorobenzenes/administration & dosage/pharmacology/therapeutic use ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & ; dosage/pharmacology/*therapeutic use ; Induced Pluripotent Stem Cells/cytology/pathology ; Lovastatin/pharmacology/therapeutic use ; Male ; Mice ; Mice, Inbred C57BL ; Phenotype ; Pyrimidines/administration & dosage/pharmacology/therapeutic use ; Receptor, Fibroblast Growth Factor, Type 3/*deficiency/*genetics ; Rosuvastatin Calcium ; Sulfonamides/administration & dosage/pharmacology/therapeutic use ; Thanatophoric Dysplasia/*drug therapy/genetics/*pathology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 2
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    Population Evolution of Helicobacter pylori through Diversification in DNA Methylation and Interstrain Sequence Homogenization (2016)
    Oxford University Press
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    Publication Date: 2016-10-14
    Description: Decoding of closely related genomes is now revealing the process of population evolution. In bacteria, population divergence appears associated with a unique set of sequence-specific epigenetic DNA methylation systems, often within restriction–modification (RM) systems. They might define a unique gene expression pattern and limit genetic flux between lineages in population divergence. We addressed the contribution of methylation systems to population diversification in panmictic bacterial species, Helicobacter pylori , which shows an interconnected population structure through frequent mutual recombination. We analyzed complete genome sequences of 28 strains collected in Fukui, Japan. Their nucleotide sequences are closely related although fine-scale analyses revealed two subgroups likely reflecting human subpopulations. Their sequences are tightly connected by homologous recombination. Our extensive analysis of RM systems revealed an extreme variability in DNA methyltransferases, especially in their target recognition domains. Their diversity was, however, not immediately related to the genome sequence diversity, except for very closely related strains. An interesting exception is a hybrid strain, which likely has conserved the methylation gene repertoire from one parent but diversified in sequence by massive acquisition of fragmentary DNA sequences from the other parent. Our results demonstrate how a bacterial population can be extremely divergent in epigenetics and yet homogenized in sequence.
    Print ISSN: 0737-4038
    Electronic ISSN: 1537-1719
    Topics: Biology
    Published by Oxford University Press
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