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Using gastrin producing G-cell and its essential gene Nkx6.3 as a model to study gastrinoma

Using gastrin producing G-cell and its essential gene Nkx6.3 as a model to study gastrinoma. CFCF Patient Education Michael Y. Choi, MD September 12, 2009. Gastric Lineages. Stomach Stem Cell. Mucous Cell. Parietal Cell. Gastroendocrine Cell. Chief Cell. Nkx6.3 Expression.

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Using gastrin producing G-cell and its essential gene Nkx6.3 as a model to study gastrinoma

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  1. Using gastrin producing G-cell and its essential gene Nkx6.3 as a model to study gastrinoma CFCF Patient Education Michael Y. Choi, MD September 12, 2009

  2. Gastric Lineages Stomach Stem Cell Mucous Cell Parietal Cell Gastroendocrine Cell Chief Cell

  3. Nkx6.3 Expression

  4. Decreased G-cell Number in the Nkx6.3-null Stomach

  5. Abrogated Gastrin mRNA Expression in Nkx6.3 Stomach

  6. Physiology Review of G- and D-cells

  7. Co-localization of Nkx6.3 and Gastrin in the Stomach

  8. Circulating gastrin levels and stomach luminal pH in Nkx6.3-/- and control animals

  9. Mutant mice strains that have altered G-cell numbers

  10. Relative expression levels of Pdx1, Pax6, and Ngn3 mRNA are unchanged in adult Nkx6.3-null stomach

  11. Nkx6.3 mRNA levels are unchanged in neonatal Ngn3-null antrum

  12. The developmental potential and epigenetic states of cells at different stages of development Stomach Pancreas Modified from Hochedlinger, K. et al. Development 2009

  13. Generating induced pluripotent stem cells by direct reprogramming • Showed that iPS cells can be generated from mouse fibroblasts by retrovirus-mediated introduction of four transcription factors: - Sox2, Oct4, Klf4, and c-Myc

  14. Yamanaka: Convert tail fibroblasts into pluripotent cells resembling embryonic stem cells by expressing 4 genes: Oct4 Sox2 Klf4 cMyc • “An Astonishing Experiment” • – Ian Wilmut, • Cloning and Stem Cells

  15. Generating insulin secreting b-cells by direct reprogramming Expressed 3 genes Ngn3, Pdx1, Mafa to generate b-cells from exocrine cells

  16. Cell Reprogamming: what’s the limit? Sox2, Oct4, Klf4, Myc Fibroblasts Stem Cells Ngn3, Pdx1, Mafa b-Cells Excocrine Cells Nkx6.3, Pdx1, Ngn3, Pax6, etc.? G-Cells (or any cell type) Non G-Cells ? Cancer Cells ?

  17. Nkx6.3 upregulates Gastrin in 293 cells

  18. Gastrinoma Endoscopic view and a nest of tumor cells in lamina propria mucosae

  19. Ramesh Shivdasani Maina Lepourcelet Anthony Romer Qiufu Ma Paul Grey Melissa Wu Andrew Leiter Yang Wang Susumu Ito Byeong-Moo Kim Daniel Podolsky Acknowledgement

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