Capable of longterm stable selfrenewal as well as differentiation

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Stem Cells

• Capable of long-term stable self-renewal as well
  as differentiation
• Pluripotent capable of producing several or
  any cell type

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Interest in Stem Cell Research

• Animal cloning
• Possible source of cells for cell-based
  therapies for many human diseases
• Possible therapeutic cloning, whereby ES cells
  could be derived from a patients cells, thus
  avoiding problems of immune rejection, and then
  coaxed into forming large quantities of the cell
  types needed for a cure.

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Fundamental Questions in Stem Cell Research

• What defines stem cells in molecular terms?
• What signaling events control stem cell
  self-renewal and differentiation?
• What does it mean to reprogram a cell?
• What is the role of stem cells in tumors?

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The First Discoveries About Stem Cells

• Production of teratocarcinoma with pluripotent
  and self-renewing properties. Leroy C. Stevens,
  Developmental Biology 21, 364-382 (1970)
• Establishment in culture of pluripotential
  embryonic stem cells (ES). M. J. Evans and M. M.
  Kaufman, Nature 292, 9 July (1981)
• Implantation of stem cells into X-irradiated
  mice. P. Hollands, Development 99, 69-76 (1987).

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The First Discoveries About Stem Cells
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The First Discoveries About Stem Cells
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The First Discoveries About Stem Cells

• Long-lived (immortal) and stable
• Capable of very wide differentiation patterns
• Able as single cells to colonize vast areas of
  chimaeras
• Capable of repairing tissues in sick recipients
• Persisting in vivo throughout lifespan
• Partially free of host-versus-graft or
  graft-versus-host reactions

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Stem Cells in Adult Organisms

• Stem cells in adult through asymmetric
  divisions, adult stem cells produce just the
  right number of differentiated cells, as well as
  daughter stem cells with properties identical to
  those from which they arose. This is true
  self-renewal.
• ES in the embryo although many cells undergo a
  similar asymmetric division with respect to
  daughter cell fate, this does not necessarily
  involve exact self-renewal. The daughter stem
  cells progressively become restricted in the
  variety of differentiated progeny they can
  produce, thereby losing developmental potential.

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Stem Cells in Adult Organisms
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Hematopoietic Lineage
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Each Stage of Differentiation Involves
Functionally Irreversible Maturation Steps
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Turning Blood Into Brain
Christopher R. R. Bjornson, Rodney L. Rietze,
Brent A. Reynolds, M. Cristina Magli, Angelo
L. Vescovi Science, 283, 22 January 1999.
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Turning Blood Into Brain
Christopher R. R. Bjornson, Rodney L. Rietze,
Brent A. Reynolds, M. Cristina Magli, Angelo
L. Vescovi Science, 283, 22 January 1999.
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Turning Blood Into Brain
Christopher R. R. Bjornson, Rodney L. Rietze,
Brent A. Reynolds, M. Cristina Magli, Angelo
L. Vescovi Science, 283, 22 January 1999.
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Transplanting a Nucleus of Adult Cells into
Embryonic Cells
I. Wilmut, A. E. Schnieke, J. McWhir, A. J. Kind
and K. H. S. Campbel Nature 385, 27 February 1997
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Transplanting a Nucleus of Adult Cells into
Embryonic Cells
I. Wilmut, A. E. Schnieke, J. McWhir, A. J. Kind
and K. H. S. Campbel Nature 385, 27 February 1997
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• How do the stem cells know their identity?
• How are self-renewal and differentiation
  controlled?
• Specialized functions required to ensure proper
  stem cell function are vested in neighboring
  differentiated cells.
• A niche is considered to be a subset of tissue
  cells and extracellular substrates that can
  indefinitely house one or more stem cells and
  control their self-renewal and progeny production
  in vivo

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Niche
Lineage mechanism asymmetric division Population
mechanism symmetric division
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Germ Cell Differentiation in Drosophila
Amy A. Kiger, Helen White-Cooper and Margaret T.
Fuller, Nature 407, 12 October 2000.
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Mitosis
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Yukiko M. Yamashita, D. Leanne Jones, Margaret T.
Fuller, Science 301, 12 September 2003.
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Yukiko M. Yamashita, D. Leanne Jones, Margaret T.
Fuller, Science 301, 12 September 2003.
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Wild Type vs Bcl-2 Transgenic Mice
Jon Domen, Samuel H. Cheshier, Irving L,
Weissman, J. Exp. Med. 191, n. 2, 17 January
2000.
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Regulation of Stem Cell Population
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Pathways in Cancer and Development
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Kazutoshi Takahashi, Koru Mitsui, Shinya
Yamanaka, Nature 423, 29 May 2003
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Kazutoshi Takahashi, Koru Mitsui, Shinya
Yamanaka, Nature 423, 29 May 2003