TheCell7e Ch18 Lecture

18 Cell Death and Cell Renewal

Overview

• Cell Death and Proliferation:

  • Balance is crucial throughout the life of multicellular organisms.

  • Processes involved:

    • Cell proliferation and differentiation.

    • Programmed cell death (apoptosis) predominantly governing death.

Importance of Cell Death

• Role in Tissues:

  • Stem cells replace lost cells in tissues.

  • Abnormalities in cell death contribute to:

    • Cancers.

    • Autoimmune diseases.

    • Neurodegenerative disorders.

  • Stem cells can proliferate and differentiate, showing promise for tissue repair.

Programmed Cell Death

• Regulation:

  • Maintains balance with cell proliferation in adults.

  • Elimination of dangerous or damaged cells (e.g., viruses).

• Developmental Role:

  • Key in removing unwanted cells:

    • Example: Larval tissue in amphibian metamorphosis.

    • Formation of fingers and toes by eliminating tissue between digits.

  • In mammalian nervous systems, up to 50% of developing neurons undergo programmed cell death.

Types of Cell Death

1. Necrosis:

   • Accidental cell death due to injury.

2. Apoptosis:

   • Programmed and active process characterized by:

     • DNA fragmentation.

     • Chromatin condensation.

     • Fragmentation of the nucleus and cell.

Recognition and Removal of Cell Types

• Apoptotic Cells:

  • Recognized and removed by:

    • Macrophages.

    • Neighboring cells.

• Necrotic Cells:

  • Swell and lyse, causing inflammation due to spilled contents.

• "Eat Me" Signals:

  • Apoptotic cells express phosphatidylserine on their surface for recognition, normally confined to the inner membrane.

Genes Involved in Apoptosis

• Studies in C. elegans:

  • Key Genes:

    • ced-3, ced-4: Required for developmental cell death.

    • ced-9: Negative regulator.

• Caspases:

  • Prototype: ced-3, part of the caspase family that cleaves target proteins to induce cell death.

Mechanisms of Apoptosis

• Caspase Activation:

  • Begins with initiator caspases, leading to effector caspases that execute cell death.

• Bcl-2 Family Proteins:

  • Regulate apoptosis:

    • Pro-apoptotic: Bax, Bak.

    • Anti-apoptotic: Bcl-2.

• Mitochondria's Role:

  • Control apoptosis through the release of cytochrome c, which activates caspase-9.

Extrinsic Pathways of Apoptosis

• Induced by signals from tumor necrosis factor (TNF) family:

  • Activates initiator caspases.

  • Cleavage leads to effector caspases' activation.

Non-Apoptotic Cell Death Mechanisms

• Autophagy:

  • Gradual turnover of cell components, activated under starvation.

• Necroptosis:

  • Programmed cell death in response to infections or injury, mediated by RIPK3 and MLKL.

Stem Cells and Tissue Maintenance

• Role in Development:

  • Cells rapidly proliferate and differentiate.

• Adult Tissue Maintenance:

  • Stem cells replace lost or damaged cells to maintain cell population.

  • Differentiated cells cannot proliferate; stem cells can.

Regenerative Tissue Mechanisms

• **Examples of Stem Cells: **

  • Fibroblasts in connective tissue respond to growth factors post-injury.

  • Endothelial cells proliferate in response to VEGF to repair vascular tissues.

  • Liver cells can undergo rapid division to replace lost tissue.

Stem Cell Properties

• Stem cells have lifelong self-renewal abilities and give rise to differentiated cells.

• They reside in specific niches that control their maintenance and differentiation.

Clinical Applications of Stem Cells

• Stem cells have potential in treating various disorders and damaged tissues:

  • Bone marrow transplants for cancer treatment.

  • Skin grafts for burns and wounds.

Pluripotent Stem Cells and Regenerative Medicine

• Pluripotency:

  • Embryonic stem cells can differentiate into various cell types, raising interest for research and therapies.

• Therapeutic Cloning:

  • Process where the nucleus of a somatic cell is transferred to an egg cell.

• Problems in Cloning:

  • Low efficiency of generating embryos and ethical concerns.

Induced Pluripotent Stem Cells (iPSCs)

• Somatic cells can be reprogrammed to become pluripotent using specific transcription factors.

• Transdifferentiation:

  • Process of directly converting one type of somatic cell to another without going through a pluripotent stage.

• Benefits:

  • Reduces risks of tumor formation and other genetic issues.