Cell Communities

From Molecules to Multicellular Organisms

  • Multicellular organisms are organized in a hierarchical manner:
    • Atomic and molecular levels: Membrane protein in neurons regulates the flow of ions.
    • Cellular level: Electrical signal travels down the length of a neuron.
    • Tissue level: Signals travel from cell to cell in nervous tissue.
    • Organ level: Nervous tissue and connective tissue in the brain aid in sight, smell, memory, and thought.
    • Organ system level: The brain and nerves send signals throughout the body to control breathing, digestion, movement, and other functions.
    • Organism level: The nervous system coordinates the functions of other systems to support life.

Tissues and Organs

  • Tissues: A group of cells that function as a unit.
    • Tissues may contain multiple cell types.
    • Animal tissues include epithelia, connective tissue, muscle tissue, and nervous tissue.
  • Organs: Structures formed by multiple tissue types that serve a specialized function.

Types of Animal Tissues

  • Nervous Tissue: Transmits signals via neurons.
    • Contains dendrites, cell bodies, and axons.
  • Muscle Tissue: Provides mechanical power for movement.
    • Skeletal muscle: Long cells, voluntary movement.
    • Cardiac muscle: Branched cells, involuntary movement.
    • Smooth muscle: Tapered cells, involuntary movement.
  • Epithelial Tissue: Forms linings and barriers.
    • Simple epithelium: Single layer of cells.
    • Stratified epithelium: Multiple layers of cells.
    • Apical side and Basolateral side
    • Basal lamina
  • Connective Tissue: Links cells together and provides mechanical support.
    • Loose connective tissue: Soft extracellular matrix; holds tissue together loosely.
    • Example: Fibroblast cell nuclei and Elastin fibers
    • Supporting connective tissue: Firm extracellular matrix; functions in structural support and protection.
    • Example: Bone (Bone cells and Matrix), Cartilage (Cartilage cells and Matrix)
    • Dense connective tissue: Fibrous extracellular matrix; holds tissue together tightly.
    • Example: Tendon (Collagen fibers and Fibroblast cell nuclei).
    • Fluid connective tissue: Liquid extracellular matrix; functions in transport.
    • Example: Blood (Red blood cell, White blood cell, Plasma).

Tissue Organization and Cell Specialization

  • Tissues are highly organized, with each specialized cell type having a specific place and primary function.
  • Differentiation and specialization occur as cells and tissues develop.
  • Differentiation is achieved through selective expression and activation/deactivation of specific proteins.
  • Cells specialize by creating unique structures (e.g., pancreatic cells exporting digestive enzymes, testis cells exporting lipid-soluble signals, cardiac muscle cells using ATP to generate the heartbeat, and leaf cells manufacturing ATP and sugar).

Cell Communities

  • Individual cells must work as part of a community to make a functional tissue and organ.
  • For a tissue to function properly, each of its cells must:
    • Maintain its specialized character and perform its function.
    • Divide only when necessary.
    • Live as long as needed.
    • Undergo apoptosis when not needed.
    • Occupy its proper space.

Development and Cell Turnover

  • Development is a highly coordinated process of cell division, growth, and differentiation.
  • A single fertilized egg continuously divides to produce a multicellular organism with many different cell types.
  • Humans have approximately 10,000,000,000,00010,000,000,000,000 cells and around 200 different cell types.
  • Cells within a tissue must be renewed regularly.
  • The rate of turnover varies depending on tissue type:
    • Intestinal epithelium: 3-6 days.
    • Epidermis: Approximately 2 months.
    • Red blood cells: Approximately 120 days.
    • Bone: Approximately 10 years.
    • Neurons: Lifetime.

Tissue Regeneration

  • Tissues may need to regenerate after an injury.
  • Regeneration involves a response to tissue damage, requiring cell proliferation to restore the damaged tissue to full functionality.

Terminal Differentiation

  • Terminal differentiation is when cells permanently become a specific type that does not divide (e.g., nerves, muscle fibers).
  • Specific signals push the cell to differentiate; common during development for dividing cells to differentiate and then stop dividing.
  • Most specialized cells are terminally differentiated.

Stem Cells

  • Stem cells are found in developing embryos and most adult tissues.
  • Features of stem cells:
    • Not differentiated.
    • Capable of dividing without limit.
    • Self-renewing.
    • Produce daughter cells that can become terminally differentiated.

Stem Cell Hierarchy

  • Totipotent: Can become all cell and tissue types, and the placenta.
    • Only the first few divisions after fertilization are totipotent.
  • Pluripotent: Can become all cell and tissue types.
    • Embryonic stem cells.
  • Multipotent: Can give rise to a specific subset of cell types.
  • iPSCs (Induced Pluripotent Stem Cells): Artificially created stem cells.

Progenitor Cells

  • A daughter cell transitioning to a fully differentiated state is called a progenitor cell or a transit amplifying cell.
  • Precursor cells refer to any ancestral cell type of a lineage.
  • Some precursor cells are unipotent stem cells (can only give rise to one cell type).

Totipotent Stem Cells

  • Form all cell types of the embryo, and the placenta, amnion, and yolk sac.
  • Only found in the zygote and up to the 4 or 8 cell stage.

Pluripotent Stem Cells

  • Can become any type of cell in the embryo.
  • Cells taken from an early embryo inner cell mass (blastocyst) can be cultured indefinitely.
  • Addition of the correct factors (growth factors, transcription factors, etc.) can push the stem cells to differentiate into any cell type.
  • Embryonic stem cells can become any type of cell.

Stem Cell Differentiation Examples

  • Development of a retina from cultured embryonic stem cells.
  • Development of red and white blood cells from hematopoietic stem cells.
    • Multipotent hematopoietic stem cell gives rise to common lymphoid precursor and common myeloid precursor.
    • Common lymphoid precursor leads to NK/T cell precursor, then NK cell, and T cell in the thymus; also leads to B cells.
    • Common myeloid precursor leads to granulocyte/macrophage progenitor and megakaryocyte/erythroid progenitor.
    • Granulocyte/macrophage progenitor leads to macrophage and dendritic cells.
    • Megakaryocyte/erythroid progenitor leads to megakaryocyte (producing platelets) and erythroblast (producing erythrocytes).

Stem Cell to Differentiated Cell Pathway

  • Stem cell divides:
    • One daughter remains a stem cell.
    • Second daughter becomes a precursor cell.
  • Precursor cells can still divide but have limited self-renewal and can only become a limited number of cell types.
  • Precursor cells divide and further differentiate, eventually undergoing terminal differentiation to become a fully functional specialized cell.

Cell Fate Choice

  • Choice of self-renewal vs. differentiation can occur in two ways:
    • Asymmetric division concentrates a key factor or factors within only one daughter cell, driving the other to a different fate.
    • Each daughter cell has an independent choice, either a 50/50 choice or driven by environmental cues and signaling from neighboring cells.

Renewal of Epithelial Cells

  • The epithelium of the intestine is arranged into villi and crypts.
    • Functional specialized cells are in the villi.
    • Stem cells are in the crypts.
  • Stem cells divide in the crypt and give rise to dividing precursors.
  • Precursors divide and then terminally differentiate into either absorptive or secretory cells.

Cell Signaling in Daughter Cell Fate

  • Paracrine Wnt signaling in the crypt maintains proliferation.
  • Contact-dependent Delta-Notch signaling drives differentiation.

Regeneration in Organisms

  • Regeneration: the reactivation of developmental mechanisms in postembryonic life to restore damaged tissues.
  • Plants can fully regenerate from a single cell.
  • Humans have limited regenerative capacity for tissues like skin, liver, GI tract epithelium, and hematopoietic tissues.

Regeneration in Flatworms (Planarians)

  • Regeneration is almost limitless in planarians.
  • The body plan will be maintained unless the cut is too fine.
  • Morphogen gradients establish the body plan for regeneration.
  • Planarians have a huge population of stem cells.
  • Radiation can affect the regeneration in planarians.

Induced Pluripotent Stem Cells (iPSCs)

  • Replacing embryonic stem cells with induced pluripotent stem cells (iPSCs).
  • Fibroblasts from adult skin biopsy are cultured.
  • Introduction of DNA encoding three key transcription regulators.
  • Creates an induced pluripotent stem cell (iPS cell).
  • Can differentiate into fat cells, neurons, macrophages heart muscle cells, etc.

iPSCs in Medicine

  • Treatment with drugs.
  • Transplantation of genetically matched healthy cells.
  • Disease-specific drugs.
  • Studying disease mechanisms.
  • Screening for therapeutic compounds.
  • Affected cell type in vitro differentiation.
  • Patient-specific iPS cells.
  • Use gene targeting to repair disease-causing mutations.