Lecture 5 Notes: Lineages and Cell Division Modes

Lecture 5 Notes

Lineages and Cell Division Modes

  • Lecturer: Stefan Thor (s.thor@uq.edu.au)
  • Lecture Objectives:
    1. Understand symmetric vs asymmetric cell division with regards to programmed (intrinsic) and niche-controlled (extrinsic) mechanisms.
    2. Learn about lineages, including stereotyped lineage trees, lineage trajectories (“flows”), and lineage analysis in human organoids.

1. Asymmetric vs. Symmetric Cell Division

Definitions
  • Symmetric Cell Division: A stem cell divides to produce two identical daughter cells, both maintaining stemness.
  • Asymmetric Cell Division: A stem cell divides to produce one daughter cell that retains stem properties and another that differentiates, leading to less “stemness”.
Mechanisms of Asymmetric Cell Division
  • Asymmetric cell divisions can be influenced by:
    • Intrinsic Programs: Internal mechanisms that dictate division outcomes.
    • Extrinsic Factors: Environmental cues from the stem cell niche that affect cell fate decisions.
    • Examples of Influence: In Drosophila, specific protein machinery ensures proper asymmetric divisions, particularly in neural stem cells.
Examples of Cell Division in Lineages
  • In the mammalian CNS, a programmed switch occurs from symmetric to asymmetric division to facilitate differentiation as development advances.
  • Decision Points for Stem Cells:
    1. To divide or not?
    2. How many divisions?
    3. Mode of division (symmetric/asymmetric)?
    4. Pattern of daughter cell divisions.

2. Lineages

  • Lineage: The complete set of cells descended from a single stem cell.
Stereotyped Lineage Trees
  • Examples of lineage trees include that of C. elegans, which exhibit invariant patterns in development. Each branch represents distinct cell fates.
  • In organisms like Drosophila, specific neural stem cells contribute to unique lineage trees, showcasing diversity in cell types produced.
Lineage Trajectories
  • Rather than a strict tree structure, lineage can exhibit "flows", meaning the path from one cell type to another can vary based on signals received post-division.
  • Myeloid and Lymphoid Stem Cells: These stem cells diversify into specific lineages based on extrinsic signals, demonstrating lineage fluidity.
Lineage Analysis in Organoids
  • Induced Pluripotent Stem Cells (iPSCs) can be used to study lineage dynamics in organoids that mimic human development, allowing for the investigation of cell state transitions and lineage relationships.
  • Novel techniques like iTracer help record lineages and determine how they evolve over time and under different conditions.

Cancer Implications

  • Asymmetric cell division plays a role in cancer development. The disruption of these pathways can lead to uncontrolled daughter cell proliferation, which is seen in overgrowth conditions associated with certain genetic mutations.

Summary Points

  1. Symmetric and Asymmetric Division: Understanding the roles and mechanisms can shed light on development and disease.
  2. Lineages: Research into stereotyped lineage trees and trajectories enhances our understanding of developmental biology, particularly through iPSC-derived organoids.
  3. Relevance in Cancer: Asymmetry in cell division may have important implications for cancer biology, linking cell division dynamics to tumorigenesis.
Future Considerations
  • How can we leverage this knowledge in regenerative medicine or organoid studies?
  • Understanding the intrinsic vs extrinsic factors in various organs can guide therapies and advancements in bioengineering.