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Genomics & Medicine http://biochem158.stanford.edu/

Genomics & Medicine http://biochem158.stanford.edu/. Stem Cells http://biochem158.stanford.edu/Stem%20Cells.html. Doug Brutlag Professor Emeritus of Biochemistry & Medicine Stanford University School of Medicine. Humbio 157/Developmental Biology 257 The Biology of Stem Cells.

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Genomics & Medicine http://biochem158.stanford.edu/

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  1. Genomics & Medicinehttp://biochem158.stanford.edu/ Stem Cells http://biochem158.stanford.edu/Stem%20Cells.html Doug Brutlag Professor Emeritus of Biochemistry & Medicine Stanford University School of Medicine

  2. Humbio 157/Developmental Biology 257The Biology of Stem Cells • The Role of stem cells in human development and potential for treating disease. • Prerequisite Humbio 2A,B or consent of instructor • Prof. Margaret Fuller and Roeland Nusse • Guest Speakers: Hank Greely, Stefan Heller, David Magnus, Anthony Oro, Theo Palmer, Thomas Rando, Renee Reijo Pera, Irving Weissman, Marius Wernig, Joanna Wysocka • Offered next year.

  3. Henry Stewart Talkshttp://hstalks.com/

  4. Differentiation of Human Tissues ZYGOTE BLASTOCYST GASTRULA Ectoderm (external layer) Mesoderm (middle layer) Endoderm (internal layer) Germ cells Skin cells of epidermis Neuron of brain Pigment cell Cardiac muscle Skeletal muscle cells Tubule cell of the kidney Red blood cells Pancreatic cell Thyroid cell Lung cell (alveolar Cell) Sperm Egg Smooth muscle (in gut) Courtesy Paul Berg

  5. Embryonic Stem Cell Cultures Courtesy Paul Berg

  6. Courtesy Paul Berg

  7. Courtesy Paul Berg

  8. Courtesy Paul Berg

  9. Basic Problems of Stem Cell Therapy • HOW TO DIRECT DIFFERENTIATION OF CELLS DOWN SPECIFIC PATHWAYS?e.g. all into muscle or all into nerve; different “cocktails”of growth factors • HOW TO OVERCOME IMMUNE REJECTION?e.g. alter histocompatibility genes; therapeutic cloning for “customized” lines • HOW TO MAKE AN ORGAN?e.g. combine different cell types in three dimensional arrangements. Courtesy Paul Berg

  10. Courtesy Paul Berg

  11. Methods to GeneratePluripotent Stem Cells Yamanaka. (2007) Cell Stem Cell Vol 1, pp 39-49.

  12. Nanog-Mediated Enhancement of Reprogramming by Fusion Yamanaka. (2007) Cell Stem Cell Vol 1, pp 39-49.

  13. Five Factors Needed to Maintain Pluripotency Yamanaka. (2007) Cell Stem Cell Vol 1, pp 39-49.

  14. Induction of Pluripotent Stem Cells (iPS) from Somatic Stem Cells Yamanaka. (2007) Cell Stem Cell Vol 1, pp 39-49.

  15. Adipose Tissue Provides iPSC Efficiently Sun et al, Proc Natl Acad Sci U S A. 2009 Sep 15;106(37):15720-5.

  16. Using CRE – Recombinase to Remove Viral Transforming DNA from iPSCs Soldner et al. Cell. 2009 Mar 6;136(5):964-77.

  17. Cre-Lox Recombination toRemove Viral DNA

  18. Inducing iPSCs usingTranscription Factor Proteins

  19. Alternate Stem Cell Fates Embryonic Stem Cells Adult Stem Cells Adult Stem Cells Courtesy Minx Fuller

  20. signals from niches maintain adult stem cells and tissues Courtesy Roel Nusse

  21. In the absence of niche signals, adult stem cells will differentiate, by default 1. Self-renewal is proliferation coupled to blocking differentiation, controlled by signals. 2.Signals are local; niches have a limited capacity and cells compete for the signals 3. The signals control tissue homeostasis, also after damage Courtesy Roel Nusse

  22. Oocyte Niche in the Drosophila Germarium Li and Xie, Ann. Rev. Dev. Biol. 2005, 605-663

  23. Cell-Cell Interactions at Oocyte Niche Li and Xie, Ann. Rev. Dev. Biol. 2005, 605-663

  24. Drosophila Spermatogonial Niche Li and Xie, Ann. Rev. Dev. Biol. 2005, 605-663

  25. Cell-Cell Interactions at the Spermatogonial Niche Li and Xie, Ann. Rev. Dev. Biol. 2005, 605-663

  26. Hair Follicle Niche Li and Xie, Ann. Rev. Dev. Biol. 2005, 605-663

  27. Intestinal Stem Cells in the Crypts • Hans Clever’s annimations

  28. Extrinsic factor(s) Niche Asymmetric stem cell divisions Courtesy Minx Fuller

  29. John Cairns: The Immortal Parental Strands Cairns (1975) Nature 255, 197

  30. Motivation for Asymmetric Strand Segregation • Adult rat contains 6x1010 cells • In its small intestine, a rat sheds over 1013 epithelial cells during its lifetime. • Requires 103 symmetric cell doublings from embryo to adult followed by 1013 asymmetric cell doublings during its lifetime • How do epithelial cells minimize mutations that lead to cancer? Cairns (1975) Nature 255, 197

  31. Asymmetric Segregation ofParental DNA Strands Rando (2007) Cell 129 1239

  32. Asymmetric Stem Cell Growth withAsymmetric Parental Strand Segregation Rando (2007) Cell 129 1239

  33. Asymmetric DNA Labeling Patterns Rando (2007) Cell 129 1239

  34. Duplicating Muscle Cell Pairs Display Asymmetric DNA Labeling Patterns Conboy et al, PLOS Biology (2007)

  35. Asymmetric Stem Cell Growth withAsymmetric Parental Strand Segregation Rando (2007) Cell 129 1239

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