Cell Differentiation Notes

Cell Differentiation

  • Mechanism where different cells arise, continuing throughout life for cell turnover, regeneration, and repair.

Modes of Cell Division

  • Symmetric proliferative: Two new proliferating cells.
  • Asymmetric: Cells with different fates.
  • Symmetric generative: Both daughter cells differentiate.
  • Plane of cell division impacts division mode; regulated by extrinsic/intrinsic factors.

Stem Cells

  • Undifferentiated, long-lived cells that self-renew and produce differentiating progeny.
  • Potency decreases over time: totipotent, pluripotent, multipotent, unipotent.
  • Adult stem cells are multipotent/unipotent, important for tissue maintenance, with limited self-renewal.

Cell Fate

  • Cells become specified, then determined to a particular fate.
  • Specified cells:
    • Develop autonomously when isolated but can change fate.
  • Determined cells:
    • Develop autonomously and retain original fate.

Regulation

  • Early development: cells regulate for removed/rearranged parts.

Gene Expression

  • Cell differentiation involves changes in gene expression; transcriptional control is key.
  • Genomic equivalence: somatic cells have the same DNA.
  • Different cell types express different combinations of genes.
  • Transcription factors regulate gene expression by binding to DNA.
  • Signalling molecules bind to receptors, indirectly altering gene expression.

Muscle Differentiation

  • Transcription factor (Mrf4) activates mesodermal progenitors to muscle fate.
  • MyoD upregulates p21, inhibiting cell cycle and starting differentiation.

Cell Fate Mechanisms

  • Cytoplasmic determinants: substances localized to affect cell commitment.
  • Extracellular signals: act on receptors, modulating transcription factor activity.
    • Induction: signals from one cell group affect another.
    • Lateral inhibition: inhibits adjacent cells from adopting the same fate.

Induction Types

  • Permissive: tissue needs a signal for successful differentiation.
  • Instructive: signal induces a change in fate.

Signal Gradients

  • Morphogens induce different responses based on concentration.

Lateral Inhibition

  • Maintains progenitor pool while ensuring appropriate cell types are formed, ensuring proper cell spacing.

Reversibility

  • Differentiation can be reversible:
    • Dedifferentiation: loss of differentiation characteristics.
    • Transdifferentiation: change into another cell type.
  • iPSCs: Yamanaka factors reprogram somatic cells to pluripotent state.