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Controlling stem cells

Controlling stem cells. CONTROLLING HUMAN PLURIPOTENT CELLS

lawrence-stephenson
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Controlling stem cells

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  1. Controlling stem cells CONTROLLING HUMAN PLURIPOTENT CELLS The generation of pluripotent human cells from embryos and adult tissues will be discussed in the context of our growing knowledge of early cell types in mammalian embryos.  Data will be presented showing that the growth and in vitro differentiation of human ES and iPS cells can be precisely controlled in vitro. IMPLICATIONS FOR HUMAN GENETICS, REGENERATION AND CANCER The precise control of human pluripotent cells allows the differences between lines to be defined.  This analysis shows that human pluripotent cells will be powerful new tools to study functional human genetics.  Two examples will be used to illustrate how stem cell technologies will advance our understanding of genetic and epigenetic control of gene expression in cancer. Josh Chenoweth, Paul Tesar & NIH stem cell facility Jong-Hoon Kim and colleagues, Seoul

  2. Cell types in the early embryo Controlling human embryonic stem cells Days after fertilization E2.5 Whole transcriptome characterization of undifferentiated hES cells Zygote Morula Mouse ES Inner Cell Mass E3.5 Trophectoderm Other labs NIH Human ES E4.5 Implant Epiblast Extra-emb. Endoderm E5.5 Mes-endoderm E6.5 Embryoid Body Ectoderm Mesoderm Endoderm

  3. Controlling differentiation of human embryonic stem cells Whole transcriptome characterization of hES cells Human ES Adult human tissue Embryoid Bodies

  4. Controlling differentiation of human iPS cells Whole transcriptome characterization of hES cells Parental Fibroblasts Adult human tissue ES iPS cells iPS EBs Embryoid Bodies

  5. Defining cancer pathways by controlling human cell states EZH1 E5.5 Epiblast Mdm2 EZH2 GNL3

  6. Glutathione S transferase (GSTT1) iPS ES BG03 GSTT1 Expression ES06 UC01 GSTT1 Copy Number Agilent: CGH Analytics used to assess copy number Polymorphic levels of gene expression – Lung & prostate cancer

  7. MGMT Promoter Methylation MGMT Expression MGMT Expression Polymorphic levels of gene expression – Glioblastoma & Teratocarcinoma MGMT MGMT +ve endothelial cells –ve melanoma brain metastasis –ve & +ve breast cancer +++ve lung cancer Ingold B, Schraml P, Heppner FL Moch H, Homogeneous MGMT immunoreactivity correlates with unmethylated MGMT promoter status in brain metstases of various solid tumors PLoS One 2009

  8. Generating Functional Human Hepatocytes HumanAlbumin 1 day CCl4 35 days after Transplantation

  9. Controlling stem cells is opening new strategies to understand & treat cancer CONTROLLING HUMAN PLURIPOTENT CELLS HUMAN GENETICS – CANCER RISK FACTORS, GLIOBLASTOMA & TERATOCARCINOMA TISSUE FUNCTION & REGENERATION The rapid advances in stem cell biology will provide the precise understanding of tumor initiation required to develop new targeted therapies for cancer.   These powerful new tools are stimulating a large global investment with important consequences for all areas of medical research.

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