Cell Turnover and Morphogenesis

Cell Turnover

• The presentation is on cell turnover, detailing growth, differentiation, and morphogenesis, as well as cell cycle, stem cells, and tissue types.
• The presentation was given by Dr N Buthelezi, Department of Anatomical Pathology, on 20/01/2025.

Growth, Differentiation and Morphogenesis

• Growth is the increase in size due to tissue synthesis.
• Types of growth include:
  • Multiplicative: Increase in cell number via mitosis, occurs in all tissues during embryogenesis.
  • Auxetic: Increase in individual cell size (e.g., skeletal muscle).
  • Accretionary: Increase in intercellular components (e.g., bone, cartilage).
  • Combined: A combination of the above types.
• Differentiation is the development of a cell's specialized function or morphology, distinguished from its parent cell.
• Gene expression is selective during differentiation, producing cells with specialized functions.

Morphogenesis

• Morphogenesis is a complex process creating the form and structure of organs (e.g., limbs, facial features).
• It involves growth and differentiation, cell movement relative to each other, and apoptosis to remove unwanted structures during embryogenesis.

Maintaining Cell Populations

• Cell proliferation is essential for:
  • Development
  • Maintaining steady-state tissue homeostasis
  • Replacing dead/damaged cells
• Cell population size depends on proliferation rate and apoptosis (cell death).
• Cell proliferation can be stimulated by physiological or pathological conditions.
• Physiological examples include endometrial tissue changes during the menstrual cycle or thyroid tissue during pregnancy.
• Pathological examples include after cell death or tissue injury.

Cell Cycle

• The cell cycle is a series of events leading to cell division.
• Phases include:
  • G1: Presynthetic growth phase
  • Restriction point
  • G1/S checkpoint
  • S: DNA synthesis
  • G2: Premitotic growth phase
  • G2/M checkpoint
  • M: Mitosis

Cell Cycle Regulation

• The cell cycle is controlled by activators (cyclins) and inhibitors (CDKIs):
  • Cyclins
  • Cyclin-dependent kinases (CDKs)
  • Cyclin-dependent kinase inhibitors (CDKIs)
• CDKs phosphorylate proteins, controlled by cyclin levels, which wax and wane.

Cell Cycle Checkpoints

• Checkpoints ensure cells with genetic imperfections do not replicate.
• G1/S checkpoint monitors DNA integrity before replication.
• G2/M checkpoint ensures accurate genetic replication before mitosis.
• Damaged DNA beyond repair triggers apoptosis or senescence.

Cyclin-Dependent Kinase Inhibitors

• p21 (CDKN1A), p27 (CDKN1B) and p57 (CDKN1C) broadly inhibit CDKs.
• p15 (CDKN2B), p16 (CDKN2A), p18 (CDKN2C) and p19 (CDKN2D) selectively affect CDK4 and CDK6.

Stem Cells

• Stem cells are undifferentiated, able to differentiate into various cell types.
• Properties include:
  • Self-renewal: Maintain stem cell pool.
  • Asymmetric division: One daughter cell differentiates, the other remains undifferentiated, maintaining self-renewal capacity.
• Types of stem cells:
  • Embryonic stem cells (most undifferentiated, present in the inner mass of the blastocyst, virtually unlimited self-renewal capacity, totipotent - can differentiate into any cell type).
  • Tissue (adult) stem cells (found within differentiated tissues, produce cells specific to that tissue, protected within stem cell niches).
    • Labile: Continuously proliferate in postnatal life, short lifespan, rapid turnover (e.g., hematopoietic cells, skin, lining cells of the digestive tract).
    • Stable: Divide infrequently under normal conditions but can rapidly divide when cells are lost (e.g., liver cells, endocrine glands, bone, renal tubules).
    • Permanent: Active stem cells do not persist long into postnatal life, cells cannot be replaced when lost (e.g., neurons, cardiac muscle cells, photoreceptors).