LW_BCH4122_Lecture6_2009Sep

LW_BCH4122_Lecture6_2009Sep - 9/28/2009 Lecture 6....

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9/28/2009 1 Lecture 6. Epigenetic reprogramming Lisheng WANG lwang@uottawa.ca Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa 1. Epigenetic reprogramming of somatic cells a. Somatic cell nuclear and Chromosome transfer b. Cell fusion c. Cell extract d. Culture-induced reprogramming e. Genetic reprogramming 2. Parthenogenesis 3. Human–animal cytoplasmic hybrid embryos, mitochondria (with an energetic debate) 4. From stem cell to progenitor and back again Epigenetic reprogramming 1. Epigenetic Reprogramming of Somatic Cells ES b. Cell fusion c. Cell extract d. Culture induced a. Nuclear/ chromosome transfer e. Genetic reprogramming Oct4+cMyc +Klf4+Sox2 (Cel 2006;126:677) Somatic cells (Nature 2006; 441: 1061-1067. Cell 2007; Science 2007; Nature 2008; Science 2008 …)
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9/28/2009 2 a. Somatic cell nuclear transfer (SCNT) reprogramming ES, NSC, T, B cells, granulocytes, etc (Cel 2006;126:652) Unsuccessful for hESC a. SCNT reprogramming – cloning timeline (Cel 2006;126:652) Nature 2007; 445 : 800-801 Rat a. Epigenetic Reprogramming of Somatic Cells Chromosome transfer - Developmental potential in vitro and in vivo after chromosome transfer from ES cells into mitotic zygotes Kevin Eggan group: NATURE 2007; 447:2007
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9/28/2009 3 b. Cell fusion reprogramming Science. 2005; 309 : 1369-1373 Dev. Dyn. 2003; 227: 504–510 EMBO J. 1997; 16: 6510–6520 Produced tetraploid hESCs (2005) c. Reprogramming by cell extract ???? Hakelien, A. M , et al. Nature Biotechnol. 2002; 20: 460–466. Hansis, C., et al. Cur . Biol. 2004; 14: 1475–1480 Taranger, C. K. et al. Mol. Biol. Cel 2005; 16: 5719–5735. Ratajczak J, et al. Leukemia 2006; 20: 1487–1495 c. Reprogramming by cell extract Hansis, C., et al. Cur . Biol. 2004; 14: 1475–1480
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4 d. Culture-induced reprogramming Hochedlinger K& Jaenisch R, Nature 2006; 441: 1061-1067 d. Culture-induced reprogramming Raf , M. Annu. Rev. Cel Dev. Biol. 19, 1–22 (2003). Stuart H. Orkin & Martin Pera, Cel Stem Cel 2007; 1: 271 Bone marrow stromal cells can give rise to multipotent adult progenitor cells (MAPCs) after in vitro culture (Jiang et al., 2002) , although it remains difficult to do so. Another multipotent progenitor cell, grown as neurosphere-like cells and termed SKPs (sk in-derived p rogenitors), can be readily isolated and expanded from skin of mouse or human origin, and then differentiated into mesodermal and neural cell types (Mil er et al, Hospital for Sick Children) . Recent data implicate the neural crest as a source of mesenchymal stem cells (Takashima et al., 2007) , and the widespread distribution of the descendants of this multipotent embryonic lineage may account for a number of observations of adult tissue cell plasticity. e. Genomic Reprogramming
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LW_BCH4122_Lecture6_2009Sep - 9/28/2009 Lecture 6....

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