Lesson 10: Cellular Development

Aug 12, 2024

Stem Cells and Differentiation

Key Concepts

  • Analogy: Compares the potential of babies to become various professionals with the potential of stem cells to specialize.
  • Stem Cells: Cells that can develop into different types of cells in the body.

Development from Zygote to Blastocyst

  • Zygote: The cell from the fusion of sperm and egg.
    • Divides by mitosis to form a blastocyst.
  • Blastocyst: A hollow ball of cells.
    • Contains the inner cell mass (ICM), which becomes the embryo.
    • ICM Cells: Pluripotent stem cells that can differentiate into over 200 cell types in the human body.

Types of Stem Cells

  • Embryonic Stem Cells: Found in the early developmental stages, responsible for creating the organism.
  • Somatic Stem Cells: Found in adults, responsible for repair and replenishment of tissues.
    • Examples: Epidermal stem cells in skin, hematopoietic stem cells in bone marrow.

Characteristics of Stem Cells

  • Self-renewal: Ability to divide and remain undifferentiated.
  • Potency: Ability to differentiate into specialized cells.
    • Unipotent: Can only become one cell type (e.g., epithelial stem cells).
    • Multipotent: Can become multiple cell types within a family (e.g., hematopoietic stem cells).
    • Pluripotent: Can become any cell type in the body (e.g., embryonic stem cells).

Mechanisms to Maintain Stem Cell Numbers

  • Obligate Asymmetric Replication: One mother cell (identical to the original) and one differentiated daughter cell.
  • Stochastic Differentiation: If a stem cell differentiates into two daughter cells, another stem cell compensates by dividing into two stem cells.

Induced Pluripotent Stem Cells (IPS)

  • Reprogramming: Introducing specific genes to specialized cells to revert them to pluripotent stem cells.
  • Applications: Core of regenerative medicine, potential to replace damaged organs with patient's own cells.

Factors Triggering Differentiation

  • Gene Expression: Stem cells express genes to remain undifferentiated.
  • Environmental Signals: Chemical signals in the environment trigger differentiation.

Cord Blood

  • Source: Blood from placenta and umbilical cord after birth.
  • Stem Cells: Contains multipotent and sometimes pluripotent stem cells.
  • Usage: Previously discarded, now preserved for its stem cells.

Summary

  • Stem cells can differentiate into specialized cells, crucial for both development and repair.
  • Different types of stem cells have varying potentials and roles in the body.
  • Mechanisms ensure the maintenance and proper function of stem cells.
  • Advances in stem cell research, like IPS cells and cord blood preservation, hold significant medical potential.

Cell-to-Cell Communication

Introduction

  • Analogy: Communicating like children in school (notes, paper airplanes, huddles, intercom)
  • Importance: Critical for evolutionary complexity and human biology

Methods of Cell Communication

Direct Cell-Cell Communication (Direct Binding)

  • Mechanism: Cells touch to communicate directly
  • Example: Macrophages and Helper T cells
    • Macrophages ingest pathogens, display antigens on MHC II proteins
    • Helper T cells recognize antigens with T cell receptors
    • Potential outcomes: Activate other immune cells (e.g., B cells) or no response

Neural Communication

  • Mechanism: Neurons communicate over short distances
  • Example: Synaptic cleft between neurons
    • Neurotransmitters released from one neuron bind to receptors on another
    • Similar to passing a paper airplane

Paracrine Signaling

  • Mechanism: Local communication between cells
  • Example: Mast cells and histamine
    • Mast cells release histamine in response to allergens
    • Histamine signals nearby cells to prepare for an allergic reaction
    • Similar to calling a huddle

Endocrine Signaling

  • Mechanism: Long-distance communication via bloodstream
  • Example: Pituitary gland releasing Growth Hormone (GH)
    • GH travels through bloodstream, reaching various body cells
    • Cells respond based on presence of appropriate receptors
    • Similar to using an intercom system

Summary

  • Key Takeaway: Cells use various methods to communicate, involving direct contact, short distances, local groups, and wide-reaching signals.

Lecture Notes: Mitochondria and Apoptosis

Overview of Mitochondria

  • Known for metabolic pathways like the Krebs cycle and the electron transfer chain.
  • Produces ATP, earning it the name "energy powerhouse of the cell".

Apoptosis (Programmed Cell Death)

  • Definition: Programmed cell death with significant roles in development and homeostasis.
  • Necrosis vs. Apoptosis:
    • Necrosis: Uncontrolled cell death due to extreme stress (infection, trauma).
    • Apoptosis: Controlled, purposeful cell death with advantages for the organism.

Importance of Apoptosis

  • Embryological Development: Example of fingers and toes; apoptosis helps shape digits by removing tissue.
  • Advantages: Helps in removing damaged cells, infected cells, and cells under stress.

Triggers of Apoptosis

  • DNA Damage: Cells with irreparable DNA damage undergo apoptosis to prevent passing on mutations.
  • Infection: Immune cells signal infected cells to undergo apoptosis.
  • Environmental Stress: Deprivation of oxygen, nutrients, and cell-to-cell connections.
  • Lack of Growth Factors: Absence of signals for cell proliferation can trigger apoptosis.
  • Reactive Oxygen Species (ROS): Unstable oxygen species (e.g., superoxide anion, hydroxide radical, hydrogen peroxide) can induce apoptosis if damage is extensive.

Role of Mitochondria in Apoptosis

  • Outer Membrane Permeability: Becomes more permeable in response to apoptotic signals.
  • BCL2 Family of Proteins: Regulate membrane permeability.
    • Pro-apoptotic proteins: Promote apoptosis.
    • Anti-apoptotic proteins: Inhibit apoptosis.
  • Cytochrome c Release: Increased permeability releases cytochrome c from the intermembrane space into the cytoplasm.
    • Function: Activates caspases.

Caspases and Apoptosis

  • Caspase Activation: Cytochrome c activates caspase enzymes in the cytoplasm.
  • Caspase Function: Proteases that break down proteins after aspartate residues using cysteine in their active site.
  • Cascade Effect: Initial caspases activate other caspases, leading to widespread protein degradation.
  • Recycling: Degraded cellular components can be phagocytosed and reused by neighboring cells.

Key Differences: Apoptosis vs. Necrosis

  • Apoptosis: Caspase-mediated, controlled, and allows recycling of cellular components.
  • Necrosis: Non-caspase mediated, uncontrolled, and usually results in cell lysis without recycling.

Lecture on Stem Cells and Cell Differentiation

Introduction to Stem Cells

  • Stem Cells: The origin of all specialized cells in the body (muscle, nerve, skin, red blood cells, etc.)
  • Specialized Cells: Muscle cells, nerve cells, skin cells, red blood cells all originate from unspecialized stem cells

Analogy with a Library

  • Library of DNA: The nucleus of each cell contains DNA, which acts like a library with all genetic instructions
  • Books/Genes: Segments of DNA called genes; these give specific instructions for making proteins
  • Gene Expression: When a cell uses certain genes, it is said to express those genes (turned on or off)

Differentiation Process

  • Pluripotent Stem Cells: Stem cells that can turn into any somatic adult body cell
  • Specialization: Process of turning on specific genes to become specialized cells (e.g., muscle cell genes for muscle cells)
  • Irreversibility: Once specialized, cells cannot de-differentiate back into stem cells naturally

Cues for Differentiation

  • Internal and External Cues: Cells decide specialization based on internal or external signals
  • Transcription Factors: Proteins that activate certain genes; crucial for differentiation

Mechanisms of Differentiation

  1. Asymmetric Segregation of Cellular Determinants

    • Initial Distribution: Transcription factors cluster in one area of the zygote
    • Division Outcome: Resulting cells have different transcription factors, leading to different gene activation and specialization
    • Terminology: Asymmetric = uneven distribution; Cellular Determinants = transcription factors/precursors
  2. Inductive Signaling (Induction)

    • Signaling Methods: Diffusion, direct contact, and gap junctions (connexons)
    • Importance: Key for the formation of body parts (limbs, ears, eyes) during embryological development

Summary

  • Goal of Differentiation: Change gene expression to turn on/off specific genes, leading to specialized cell formation

Lecture Notes: Types of Cells and Cellular Senescence

Types of Cells in the Body

Mitotic Cells

  • Definition: Cells capable of dividing through mitosis.
  • Examples:
    • Epithelial cells (skin)
    • Fibroblast cells (organ scaffolding like kidneys and liver)
    • Endothelial cells (line blood vessels)
  • Function: Replenish and regenerate tissues.
  • Include: Some stem cells (precursors).
  • Key Feature: Undergo mitosis.

Post-Mitotic Cells

  • Definition: Cells incapable of undergoing mitosis; also called non-mitotic cells.
  • Examples:
    • Neurons (brain and nervous system)
    • Heart muscle cells
  • Function: Limited ability to repair or regenerate tissues.
  • Regeneration: Slow, relies on tissue-specific stem cells.

DNA Replication and Telomeres

  • Mitosis and DNA Replication: DNA must be copied for daughter cells.
  • Eukaryotic DNA: Linear strands with telomeres at both ends.
  • Telomeres: Caps that protect DNA from damage during replication (don’t code for proteins).
  • DNA Polymerase Limitation: Does not copy DNA to the end, causing telomeres to shorten with each replication.
  • Telomere Shortening: Limits cell divisions to around 60-70 cycles (Hayflick limit).

Cellular Senescence

  • Definition: State where a cell stops dividing due to short telomeres or DNA damage.
  • Replicative Senescence: When a cell reaches its Hayflick limit due to telomere shortening.
  • Features: Changes in gene expression, appearance, and response to surroundings.
  • Purpose: Prevents DNA damage from being passed on, reducing cancer risk.
  • Triggers: Telomere dysfunction, DNA mutations, toxin damage.

Implications of Senescent Cells

  • Pros: Helps prevent tumors and cancer by stopping cell division.
  • Cons: Reduced tissue regeneration with age, possible link to age-related diseases (e.g., cataracts).
  • Active Research: Ongoing studies to better understand these cells.

Senescence in Different Cell Types

  • Mitotic Cells: Can undergo replicative senescence.
  • Post-Mitotic Cells: Do not replicate but can become senescent due to DNA damage.

Cell Division Capacity Graph

  • Y-Axis: Cell division capacity.
  • X-Axis: Number of doublings.
  • Somatic Cells: High initial capacity, decreases with each division due to telomere shortening.

Stem Cells

  • High Division Capacity: Maintains high capacity regardless of doublings.
  • Reason: Presence of enzyme telomerase, which replenishes telomeres.
  • Cancer Connection: Somatic cells can mutate to express telomerase, evade senescence, and potentially form tumors.

Lecture Notes: Cell Movement and Migration

Introduction

  • Cells move around in our bodies to perform various functions.
  • Red blood cells are pumped by the heart; they don't swim.
  • Other cells can move independently, both in the bloodstream and through tissues.
  • Cell movement is vital for development (forming tissues/organs) and immune function in adults.

Sperm Cells Movement

  • Sperm cells move using a flagellum (tail).
  • Flagellum made of microtubule proteins and dynein proteins.
  • Importance: Sperm needs to move to reach the egg for fertilization.
  • Flagella in bacteria and archaea differ in structure and function.

White Blood Cells Movement

  • Example: Neutrophils (a type of white blood cell).
  • Neutrophils travel in the bloodstream and respond to infection signals.
  • Movement involves sticking to endothelium, rolling along, and moving between endothelial cells to reach tissues.
  • Movement driven by the cytoskeleton (cell skeleton).

Theories of Cell Movement

1. Cytoskeletal Model of Movement

  • Actin Polymerization: Actin proteins rapidly polymerize at the cell's leading edge, pushing it forward.
  • Microtubules: Located at the back, acting as a rudder (steering) or anchor (stopping movement).
    • Flexible microtubules: steer the cell.
    • Fixed microtubules: anchor the cell.

2. Membrane Flow Model

  • Endocytosis and Exocytosis: Plasma membrane bits internalized as vesicles, then move to the front and exocytose.
  • Types of Vesicles:
    • Plasma membrane vesicles: extend the leading edge.
    • Integrin-containing vesicles: anchor the cell membrane to help it crawl.
  • Net effect: Cell moves in a specific direction by alternating between extending and anchoring.

Conclusion

  • Understanding cell movement mechanisms is crucial for insights into development, immune response, and potential disease treatment (e.g., infertility due to immotile sperm).