Chapter 22: Stem Cells and Cell Death

Stem Cells:
- Definition: Cells that can proliferate indefinitely.
- Key Processes:
- Symmetric Cell Division: Results in two identical stem cells or two differentiated cells.
- Asymmetric Cell Division: One stem cell is produced along with one differentiated cell, maintaining the stem cell population.
- Cell Growth: Increases cell numbers, with some cells destined for differentiation.
Environmental Influence: During development or in response to signals, cells may undergo programmed cell death (apoptosis).

Fertilization: Unification of the genome where one sperm fertilizes one egg, leading to the formation of a totipotent fertilized egg.
- Totipotent Cell: Potential to develop into all cell types of the body and supportive placental cells for embryonic growth.
What is a Stem Cell?:
- Definition: A stem cell can proliferate indefinitely and is capable of self-renewal, generating specific types of more specialized cells.
- Differentiation Limitations: Differentiated cells can divide only a limited number of times and typically do not proliferate.

Embryonic Stem Cells (ESCs):
- Characterized as pluripotent (cannot form placenta).
- Cell fate is progressively restricted starting from the two-cell stage to the blastocyst stage.
Development Stages:
- Two-cell stage → Four-cell stage → Eight-cell stage → Compacted morula → Blastocyst (64 cells; formation of trophectoderm and inner cell mass).
- Inner Cell Mass: Will later form three germ layers:
- Ectoderm: Central nervous system, skin.
- Mesoderm: Muscle, connective tissue, skeleton.
- Endoderm: Gut epithelia.

Control Factors for Pluripotency:
- Three transcription factors are key in maintaining ESC identity: Nanog, Sox2, and Oct4.
- Regulatory Mechanisms:
- Activation of self-renewal genes and repression of genes inducing specific differentiation.
- Epigenetic Factors:
  - DNA Methylation and Histone Code (Polycomb Group proteins) regulate pluripotency.
  - Role of Long Noncoding RNAs and Micro-RNAs in gene regulation.

Induction of iPS:
- Somatic cells can be reprogrammed into iPS cells using four transcription factors: Sox2, Oct4, KLF4, and Myc.
- This process turns on Nanog during reprogramming.
Therapeutic Potential:
- iPS cells can be created from patient-derived cells with no incompatibility issues for therapy. They can restore or replace damaged tissues and can be used to study diseases and screen drugs.

Stem Cell Niches: After embryogenesis, stem cells are usually unipotent or multipotent rather than pluripotent.
Types and Roles:
- Germ-Line Stem Cells: In ovaries of fruit flies; differentiated pathways influenced by neighboring cells (signals).
- Intestinal Stem Cells: Regenerate intestinal lining every 5 days; maintain ability to proliferate; signals such as Wnt and Notch pathways are crucial.
- Hematopoietic Stem Cells: Located primarily in bone marrow; signals from stromal cells support self-renewal and differentiation.

Apoptosis Characteristics:
- Key features include cell shrinkage, chromatin compaction, nuclear fragmentation, and cell fragmentation leading to phagocytosis.
Comparison with Necrosis:
- Necrosis causes inflammation and is linked to acute injuries, resulting in cell swelling and bursting; while apoptosis is a controlled, non-inflammatory process.

Caspases: Proteases involved in the initiation and execution of apoptosis, activated through proteolytic processing, leading to an irreversible cascade.
Role of Bcl-2 Family Proteins:
- Pro-survival and pro-apoptotic proteins regulate mitochondrial channels that govern Cyt c leakage into the cytosol, key for signaling apoptosis.

Death Receptors: Activated by signals such as TNFα and Fas ligands; this leads to the clustering of procaspase-8 proteins, which initiates the apoptosis cascade.

Necroptosis occurs when extrinsic apoptosis pathways are blocked, leading to cell and organelle swelling and potential rupture of the plasma membrane, contributing to inflammation.