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Unformatted text preview: y enable induced pluripotent stem cells to be readily established and used for patient-specific transplantation therapy. KEY TERMS
COMPANION WEBSITE SUMMARY
Visit the website that accompanies The Cell (www.sinauer.com/cooper5e) for animations, videos, quizzes, problems, and other review material. programmed cell death, necrosis, apoptosis PROGRAMMED CELL DEATH
The Events of Apoptosis: Programmed cell death plays a key role in both the maintenance of adult tissues and embryonic development. In contrast to the accidental death of cells from an acute injury, programmed cell death takes place by the active process of apoptosis. Apoptotic cells and cell fragments are then efficiently removed by phagocytosis. Genes responsible for the regulation and execution of apoptosis were initially identified by genetic analysis of C. elegans. See Website Animation 17.1 caspase, apoptosome Caspases: The Executioners of Apoptosis: The caspases are a family of proteases that are the effectors of apoptosis. Caspases are classified as either initiator or effector caspases, and both function in a cascade leading to cell death. In mammalian cells, the major initiator caspase is activated in a complex called the apoptosome, which also requires cytochrome c released from mitochondria. Central Regulators of Apoptosis: the Bcl-2 Family: Members of the Bcl2 family are central regulators of caspase activation and apoptosis. Some members of the Bcl-2 family function to inhibit apoptosis (antiapoptotic) whereas others act to promote apoptosis (proapoptotic). Signals that control programmed cell death alter the balance between proapoptotic and antiapoptotic Bcl-2 family members, which regulate one another. In mammalian cells, proapoptotic Bcl-2 family members act at mitochondria, where they promote the release of cytochrome c, leading to caspase activation. Caspases are also regulated directly by inhibitory IAP proteins. Bcl-2, IAP This material cannot be copied, reproduced, manufactured, or disseminated in any form without express written permission from the publisher. 2009 Sinauer Associates, Inc. UNCORRECTED PAGE PROOFS
CELL DEATH AND CELL RENEWAL 29 SUMMARY
Signaling Pathways that Regulate Apoptosis: A variety of signaling pathways regulate apoptosis by controlling the expression or activity of proapoptotic members of the Bcl-2 family. These pathways include DNA damage-induced activation of the tumor suppressor p53, growth factorstimulated activation of PI 3-kinase/Akt signaling, and activation of death receptors by polypeptides that induce programmed cell death. Alternative Pathways of Programmed Cell Death: Autophagy and regulated necrosis provide alternatives to apoptosis for induction of programmed cell death. KEY TERMS
p53, PI 3-kinase, Akt, tumor necrosis factor (TNF) autophagy STEM CELLS AND THE MAINTENANCE OF ADULT TISSUES
Proliferation of Differentiated Cells: Most cells in adult animals are arrested in the G0 stage of the cell cycle. A few types of differentiated cells, including skin fibroblasts, endothelial cells, smooth muscle cells, and liver cells are able to resume proliferation as required to replace cells that have been lost because of injury or cell death. Stem Cells: Most differentiated cells do not themselves proliferate but can be replaced via the proliferation of stem cells. Stem cells divide to produce one daughter cell that remains a stem cell and another that divides and differentiates. Stem cells have been identified in a wide variety of adult tissues, including the hematopoietic system, skin, intestine, skeletal muscle, brain, and heart. Medical Applications of Adult Stem Cells: The ability of stem cells to repair damaged tissue suggests their potential use in clinical medicine. Adult stem cells are used to repair damage to the hematopoietic system in hematopoietic stem cell transplantation, and epidermal stem cells can be used for skin grafts. However, clinical applications of adult stem cells are limited by difficulties in isolating and culturing these cells.
stem cell, niche hematopoietic stem cell transplantation, bone marrow transplantation EMBRYONIC STEM CELLS AND THERAPEUTIC CLONING
Embryonic Stem Cells: Embryonic stem cells are cultured from early embryos. They can be readily grown in the undifferentiated state in culture while retaining the ability to differentiate into a wide variety of cell types, so they may offer considerable advantages over adult stem cells for many clinical applications. Somatic Cell Nuclear Transfer: Mammals have been cloned by somatic cell nuclear transfer in which the nucleus of an adult somatic cell is transplanted into an enucleated egg. This opens the possibility of therapeutic cloning in which embryonic stem cells would be derived from a cloned embryo and used for transplantation therapy of the donor of the adult nucleus. Although many obstacles need to be overcome, the possibility of therapeutic cloning holds great promise for the development of new treatments for a variety of devastating diseases. Induced Pluripotent Stem Cells: Adult somatic cells can be converted to pluripotent stem cells in culture by four key transcription factors, pote...
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