2. • The cells of a multicellular organism are members of a
highly organized community.
• The number of cells in this community is tightly
regulated-not simply by controlling the rate of cell
division, but also by controlling the rate of cell death.
• What is Apoptosis? In multicellular organisms, cells
that are no longer needed or are a threat to the
organism are destroyed by a tightly regulated cell
suicide known as apoptosis (programmed cell death).
3. What purpose does this massive programmed cell death
serve?
• Mouse paws are sculpted by cell death during
embryonic development; They start out as spade-like
structure, and the individual digits separate only as
the cells between them die.
4. Figure; Sculpting the digits in the developing mouse paw by apoptosis. (A) The paw in this mouse
embryo has been stained with a dye that specifically labels cells that have undergone apoptosis. The
apoptotic cells appear as bright green dots between the developing digits. (B) This interdigital cell
death eliminates the tissue between the developing digits, as seen one day later, when few, if any,
apoptotic cells can be seen.
5. • In other cases cells die when the structure they form is
no longer needed. When a tadpole changes into a frog,
the cells in the tail die, and the tail, which is not
needed in the frog, disappears.
6. Figure; Apoptosis during the metamorphosis of a tadpole into a frog. As a tadpole changes into a frog,
the cells in the tadpole tail are induced to undergo apoptosis; as a consequence, the tail is lost. All the
changes that occur during metamorphosis, including the induction of apoptosis in the tail, are
stimulated by an increase in thyroid hormone in the blood.
7. Apoptosis is mediated by an intracellular proteolytic
cascade.
Caspases: a family of proteases that have a cysteine at
their active site and cleave their target proteins at
specific aspartic acids.
A. Caspases are synthesized in the cell as inactive
precursors, or procaspases, which are usually activatec
by cleavage at aspartic acids by other caspases.
8.
9. B. Once activated, caspases cleave, and thereby activate,
other procaspases, resulting in an amplifying proteolytic
cascade.
• Some cleave the nuclear lamins, causing the
irreversible breakdown of the nuclear lamina.
• Another cleaves a protein that normally holds a
DNAse inactive.(Freeing the DNAse to cut up the DNA
in the cell nucleus)
10.
11. Apoptosis activation from outside the cell by the
activation of cell surface death receptors (Extrinsic
Pathway)
• For example: Fas ligand on the surface of killer
lymphocytes and the death receptor protein Fas on
the surface of the target cell.
• Some stressed or damaged cells kill themselves by
producing both the Fas ligand and the Fas protein.
12.
13. Apoptosis activation from inside the damaged or stressed
cells (Intrinsic Pathway)
• Mitochondria are induced to release the electron carrier
protein cytochrome c into the cytosol.
• It binds and activates an adaptor protein called Apaf-1.
• DNA damage, can trigger apoptosis. This response usually
requires p53, which can activate the transcription of
genes that encode proteins that promote the release of
cytochrome c from mitochondria. These proteins belong
to the Bcl-2 family.
I work for the California Institute for Regenerative Medicine, a state government agency that funds stem cell research. We don’t actually do the research, but we decide what scientific projects in California are worth spending money on and make sure that researchers are using the money in a way that will lead to stem cell cures for the people of California. Our agency’s mission is to “turn stem cells into cures”.
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Embryonic stem cells (ESCs) have an unusual cell cycle structure with a short G1 phase and with the largest proportion of cells in the S phase. During differentiation, the ESC cycle is readily remodeled and a prominent G1 phase is established. Recently, prolongation of G1 phase has been shown to be sufficient to induce ESC differentiation and, on the other hand, remodeling of cell cycle to an ESC-like cell cycle has been found to be a crucial and rate-limiting step in the process of reprogramming of differentiated cells to induced pluripotent stem cells. The specific structure of ESC cycle has been suggested to be a general requirement for pluripotency and self-renewal and existence of several links between cell cycle machinery and core pluripotency factors has been proposed.
Embryonic stem cells (ESCs) have an unusual cell cycle structure with a short G1 phase and with the largest proportion of cells in the S phase. During differentiation, the ESC cycle is readily remodeled and a prominent G1 phase is established. Recently, prolongation of G1 phase has been shown to be sufficient to induce ESC differentiation and, on the other hand, remodeling of cell cycle to an ESC-like cell cycle has been found to be a crucial and rate-limiting step in the process of reprogramming of differentiated cells to induced pluripotent stem cells. The specific structure of ESC cycle has been suggested to be a general requirement for pluripotency and self-renewal and existence of several links between cell cycle machinery and core pluripotency factors has been proposed.