10.多能干细胞与重编程124.ppt

Treatments of Klinefelter syndrome Testosterone treatment Intracytoplasmic sperm injection (ICSI) treatment --rare Pathogenetic mechanism: unclear Expert Rev. Mol. Diagn. (2010) 10: 765–776 Sex Dev (2010) 4:249–258 DNA FISH of KS-fibroblast cells (47,XXY) X Y DNA FISH 基因型检查 X Y X Y ks-iPSC-1 ks-iPSC-4 There is not detectable difference between iPSCs established from normal or patient samples N-iPSC-1 KS-iPSC-1 KS-iPSC-4 KS-iPSC-4 KS-iPSC-8 KS-iPSC-11 Ma et al. Journal of Biological Chemistry 287: 38970-38979, 2012 N-iPSC-1 KS-iPSC-1 KS-iPSC-4 KS-iPSC-4 KS-iPSC-8 KS-iPSC-11 Patient iPSCs could be induced into germ cell lineage differentiation Premeiotic Germ Cells BMPs RA Spontaneous Differentiation Meiosis R115866+FRSK+LIF+FGF2 Meiotic Germ Cells hESCs or hiPSCs DAZ+DAZL+BOULE in vitro Germ cell differentiation-expression of VASA after BMP induction N-iPSC-1 KS-iPSC-1 KS-iPSC-4 d0 d7 d14 X chromosome inactivation occurs in patient iPS cells H3K27me3 macroH2A1 KS-fs KS-iPSC-1 KS-iPSC-4 KS-iPSC-8 KS-iPSC-11 H3K27me3 MacroH2A1 Dysregulation of X linked genes Up-regulated Genes (fc=2) Down-regulated Genes (fc=2) XCI is possibly incomplete Location No. of Genes Up-regulation (31) X Chromosome 11 Y Chromosome 1 Autosomes 19 Down-regulation (9) X Chromosome 0 Y Chromosome 0 Autosomes 9 Gene ontology analysis of the differentially expressed genes between XXY cells and XY cells P Value 0.5, fc=1.5 Potential applications of KS patient iPS cells Study the mechanisms of development of clinical symptoms in KS patients; Explore the possibility of using KS iPS cells to differentiate into normal germ cells for the treatment * * * * Dolly the sheep was born after 277 eggs were used for SCNT, which created 29 viable embryos. Only three of these embryos survived until birth, and only one survived to adulthood.[9] First mammal to be cloned from an adult somatic cell. a cell taken from a specific part of the body could recreate a whole individual. * * * Induced Pluripot