Differentiated Cells and the Maintenance of Tissues

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Differentiated Cells and the Maintenance of
Tissues

• 311 304 Cell Molecular Biology

Jirapat Chunthapong September, 2006
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1. ????????????????? Differentiated

• Differentiation ??? ??????????????????????????????
  ??????????????????????????????????????????
  (specialized cells)
• ??????????????????????????????????????????????
  ??????????? ????????????????????????
  differentiated ???????????????????????????????????
  ??????
• ?????????????? (organization) ????????????????????
  ??????????????????????????????????????????????????
  ???????????

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Three key factors maintain the cellular
organization of tissues
Alberts Essential Cell Biology, 2004
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Mammalian skin is made of a mixture of cell types
Alberts, et al. 2002
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• ??????????????????????????????????????????????????
  ???????????????????????????? ?????????????????????
  ????????????????????????????????????
• ??????????????????????????????????????????????????
  ?????????????????????? ???????????????????????????
  ??????????????????????????????????????? cell
  memory
• Specialized cells ????????????????????????????????
  ??????? ??????????????????????????????????????????
  ????????????????????????????????????
  ???????????????????????????????????????

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• ???????????????????????????????? differentiated
  ??? ??????????????????????????????????????????????
  ?????? ??????????????????????????????
• ???????? 1 ??????????????????????????????????????
  ??????????????????????????????????????????????????
  ?????
• ???????? 2 ??????????????????????????????????????
  ???????????????????????????????????
  ??????????????????????????? ECM
• ???????????????????????????????????????????
  ??????????????????????????????????????????????????
  ????? ????????????????????????? differentiated
  cells ????????????????? stem cells

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2. ???????????????????????????????????????
Differentiated Cells

• ??????????????????????????????????????????????????
  ?? differentiated cells ?????? ???????? ???
  ?????????????????
• ????? hepatocytes ????????????????????? 1 ??
  (slow turnover)
• ?? homeostatic mechanism ??????????????
  hepatocytes ???????? ?????????????????????????????
  ?????????????
• ???????? ?????????????? ???? ????????????????????
  ???????? 1 ??? hepatocytes ?????????????????????
  ????????

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Alberts, et al. 2002
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• ?????? hepatocytes ?????????????? ???? stem cells
  ?????????????????? ???????????????????????????????
  ??????????? hepatocytes ??????????
• ??????????????????????????????????????????????????
  ????????????? hepatocytes ??????????????
  hepatocyte growth factor (HGF)
• HGF ????????????????????????????? hepatocytes
  ????? tissue culture ???????????????? liver
  damage ????????? HGF ???????????????????????
  (????????????????)

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3. ??????????????????????????????????????????
(Stem Cells)

• ????????????? differentiated cells
  ??????????????????????????????????????
  ???????????????????????????????? terminally
  differentiated
• ???????????????????? terminally differentiated
  cells ??????????????????? precursor cells
  ?????????????? stem cells
• Stem cells ??????????????? ???????????????

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Alberts Essential Cell Biology, 2004
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Alberts Essential Cell Biology, 2004
Renewal occurs continuously in the lining of the
adult intestine
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Alberts, et al. 2002
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Alberts Essential Cell Biology, 2004
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Alberts Essential Cell Biology, 2004
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Alberts Essential Cell Biology, 2004
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4. ??????????????

• ????????????????????????????? 2 ??????
• Necrosis killed by injurious agents
• Apoptosis induced to commit suicide (programmed
  cell death)
• ???????? necrosis ????????? ?????????????
  ????????
• ???????? apoptosis ??????????????????????????????
  ????????????????????????????????????????????

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4.1 Necrosis

• ?????????? Mechanical damage
• ??????????????????????????????????????
• ??????????????????????????????????????????????????
  ???????????????????????????????????????????????
• ??????????????????????????????????
• ????????????? (inflammation) ?????????????????

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4.2 Apoptosis

• Apoptosis (???????? ?????? ??????? ???? ????????)
• ???????????????????
• ?????????????????????????????????????????????
  ??????????????????????????????????????????????????
  ???
• ??????????????????????? survival signal
  ?????????? death signal ????????????
• ????????????? apoptosis ???? common molecular
  pathway ??????????????????????????????????

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• ??????????????????????????????????????????
• Cell body shrinks, nucleus condenses, DNA undergo
  fragmentation ? ?????????? apoptotic bodies
  (??????????????????????????????????)
• ??????????????????????????????????????????????????
  ??????????
• ??????????????????????????????????????????????????
  ??????????????????????????????

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Ultrastructural features of cell death by
apoptosis
Normal
Apoptosis
Lodish et al, 2000
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(No Transcript)
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Alberts Essential Cell Biology, 2004
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Cell,Vol.103,273282,October13,2000
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Caspases

• Cysteine proteases (an enzyme family)
• Selectively cleave proteins at sites just
  C-terminal to aspartate residues
• Intracellular targets nuclear lamina,
  cytoskeleton, etc.
• Activation of caspases is a common feature of
  most (if not all) cell death programs

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Current Models of the Intracellular Pathways
Leading to Cell Death or Cell Survival
Lodish et al, 2000
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• ?????????????? trophic factor ?????? Bad ????????
  pro-apoptotic factor ???????????? anti-apoptotic
  proteins 2 ???? ??? Bcl-2 ??? Bcl-xl
  ???????????????????????????????????????
• ?????? Bad ?????? Bcl-2 ??? Bcl-xl ???????????
  Bcl-2 ??? Bcl-xl ?????????????????????????????
  Bax ???
• Bax ???? pro-apoptotic protein ????????????????
  homo-oligomeric channels ????????? ion flux ?????
  cytochrome C ?????????????????????????????????????
  ??????????????????????????????? ?????????????
  adaptor protein ???? Apaf-1 ?????????????????
  caspase activation ??????????? cell death

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• ??????????? trophic factor ???? growth factor
  ??????????????????????????? PI-3 kinase
  ??????????????????????????????????????????? Akt
• Akt ????????? phosphorylation ????????? Bad
• Phosphorylated Bad ??????????????????????? 14-3-3
• ???????????? Bad ???????????????????? cytoplasm
  ???????????? Bcl-2 ??? Bcl-xl ????????????????????
  ??? Bax ??????????????? ??????????????????????????
  cytochrome C ???????? caspase activation