Lecture 4 Notes on Stem Cells and Hox Code

Types of Stem Cells

Adult Stem Cells (ASCs):

• Maintain an undifferentiated state for tissue regeneration, allowing for cell replacement in various tissues throughout the body.

• Found in specialized niches within tissues such as bone marrow, skin, and the lining of the gut, where they play critical roles in maintaining homeostasis and healing.

Embryonic Stem Cells (ESCs):

• Derived from the inner cell mass of the blastocyst, these cells are pluripotent, meaning they can differentiate into any cell type, including neurons, muscle cells, and blood cells, which makes them invaluable for research and therapy.

• ESCs can proliferate indefinitely in culture while maintaining their pluripotent status, allowing scientists to generate large quantities of specific cell types.

Induced Pluripotent Stem Cells (iPSCs):

• Mature somatic cells, such as skin or blood cells, are reprogrammed to a pluripotent state using specific transcription factors identified by Shinya Yamanaka and colleagues in 2006.

• iPSCs provide an ethical alternative to ESCs, as they can be generated from a patient’s own cells, reducing the risk of immune rejection during potential therapeutic applications.

Cell Differentiation

Cells progressively differentiate into specialized forms as development proceeds, a process largely determined by gene expression and cellular environment.

• Differentiation involves:

  • Germ Cell Layers: Cells are partitioned into three germ layers: Ectoderm (develops into skin and nervous system), Mesoderm (forms muscles, bones, and blood), and Endoderm (gives rise to internal organs such as the gut and lungs).

  • Irreversibility of Cell Fate: Once a cell's fate is determined through differentiation signals, it typically cannot revert to a previous pluripotent state, entailing significant implications for regenerative medicine and cellular therapy.

  • Asymmetric Cell Division:

  • This process allows one daughter cell to remain a stem cell while the other begins to differentiate into a specialized cell type, which is crucial for tissue homeostasis and regeneration.

Stem Cell Research and Applications

The potential for regenerative therapies is vast, with ongoing research focusing on treating diseases such as neurodegenerative disorders (e.g., Parkinson's disease), muscle degeneration (e.g., muscular dystrophy), diabetes (by regenerating insulin-producing cells), and spinal cord injuries.

• ESCs can mature into required cell types when exposed to specific growth factors, making them valuable in biomedical research, drug testing, and potentially cell replacement therapies.

Ethical Considerations

Challenges associated with the use of human embryonic stem cells include ethical concerns regarding the destruction of embryos, which has sparked significant debate in the scientific community and among policymakers.

• A need for social discussion regarding the acceptability of certain practices in stem cell research is paramount. Regulatory frameworks must balance potential medical benefits with ethical considerations, ensuring responsible research practices.

Positional Information and the Hox Code

Concept of Positional Code:

• Cells respond to positional information through division, differentiation, changes in shape, movement, and apoptosis (programmed cell death), which are crucial for proper development and organization of tissues.

Morphogenesis: The process that results in shape and structural formation is influenced by cell responsiveness to this spatial context, impacting the overall architecture of an organism during development.

Hox Genes:

• Homeotic genes are involved in specifying identity along anterior-posterior (A/P) and dorsal-ventral (D/V) axes, providing essential information for the correct segmentation and development of body structures.

• Understanding positional information in model organisms like Drosophila has led to insights on functional conservation of similar genetic mechanisms in vertebrates, underscoring the evolutionary significance of Hox gene functions.

• Collinearity, the arrangement of Hox genes along the chromosome, parallels their expression along the body axis, ensuring precise regulation needed for proper development.

• Homeobox: The conserved 180bp DNA sequence found in homeotic genes encodes a 60 amino acid homeodomain, a protein that binds to DNA and regulates gene expression critical for developmental processes.

Summary of Key Concepts

1. Stem Cell Types: Adult, embryonic, and induced pluripotent stem cells, all with unique properties related to their differentiation capabilities and potential applications in medicine.

2. Cell Differentiation: Involves germ layer assignment, gene activation, and the commitment to specific cell types, demonstrated in the context of both embryonic development and tissue repair.

3. Hox Genes and Positional Information: Adopt a combinatorial approach to develop positional identity, regulating morphogenesis through precise gene expression patterns along the body axes.

4. Applications and Ethics: Stem cell research holds implications for regenerative medicine, coupled with ethical dilemmas surrounding the use of human embryonic stem cells and the need for responsible research practices.