Cell Differentiation and Variation

• Stem Cells and Potency

  Stem cells are unspecialised cells which have the ability to become specialised cells, such as heart cells or neurons. The process by which a stem cell is converted from an unspecialised cell to a specialised cell is called cell differentiation. Stem cells have an unlimited capacity to divide and can produce lots more stem cells by mitosis.
• The ability of stem cells to undergo differentiation is referred to as potency there are different levels of potency:

  • Totipotent: totipotent cells have the ability to divide into any type of cell (including the extraembryonic cells which make up the placenta and umbilical cord).
  • Pluripotent: pluripotent cells can divide into any type of cell except the extraembryonic cells.
  • Multipotent: these cells can divide into a handful of different cell types
  • Unipotent: these cells can only divide into one type of cell
• All cells of our body contain exactly the same set of genes but can have very different structures and functions in our body
• Gene expression


  The activation (and deactivation) of different genes in cells results in the production of different proteins, causing cells to have different structures and functions
• Gene expression


  1. Certain genes are activated

  2. Activated genes are transcribed into mRNA

  3. mRNA is translated into protein

  4. Proteins modify the cell by changing its structure and controlling cellular processes

  5. Cell becomes specialised
• Transcription Factors

  The activation and deactivation of genes is carried out by proteins called transcription factors (TFs). TFs which activate genes are called activators whereas TFs which deactivate genes are referred to as repressors. Activators can work by binding to the beginning of the gene (the promoter region) and helping RNA polymerase to bind and transcribe the gene. Repressors can work by binding to the gene and blocking RNA polymerase from binding.

  
• Operons

  In prokaryotes, transcription factors bind to regions of DNA called operons. An operon is a section of DNA that contains a cluster of genes which are controlled by a single promoter (regulatory region). Operons contain the following elements:

  • Structural genes these code for useful proteins such as enzymes
  • Control elements these contain a promoter region where RNA polymerase can bind and an operator region where transcription factors can bind
  • Regulatory gene these codes for transcription factors (activators or repressors).

  
• Lac Operon


  A group of genes in E. coli that are responsible for the digestion of lactose
• E. coli


  • They feed on glucose
  • They can digest lactose when glucose is not available
  • They only produce the enzymes to digest lactose when glucose is absent and lactose is present, to avoid wasting energy and resources
• Lac operon


  The genes which produce the enzymes to respire lactose
• Regulation of the lac operon

  1. When lactose is absent, a regulatory gene (lacI) produces a protein called the lac repressor

  2. The lac repressor is a transcription factor which binds to the operator region

  3. This blocks RNA polymerase from binding to the promoter region so the structural genes are not transcribed
• Lac operon regulation


  1. Lactose binds to repressor

  2. Repressor changes shape

  3. Repressor can no longer bind to operator

  4. RNA polymerase binds to promoter

  5. RNA polymerase transcribes lacZ, lacY and lacA
• lacZ


  Codes for beta-galactosidase enzyme which breaks down lactose into glucose and galactose
• lacY


  Codes for lactose permease protein which transports lactose into the cell
• The function of the lacA gene and its exact role in digesting lactose is still not sure
• Stem cells


  Cells that can develop into different cell types in the body
• Stem cell transplants


  1. Given to patients with leukaemia

  2. Leukaemia destroys stem cells

  3. Bone marrow transplants replace lost stem cells
• Growing organs from stem cells

  1. Develop ways to grow whole organs

  2. Transplant organs to replace damaged or diseased organs

  3. Help those waiting for organ donations
• Adult stem cells (ASCs)


  • Found in bone marrow of adults
  • Have more limited potency
  • Can only develop into a limited number of cell types (multipotent)
• Embryonic stem cells (ESCs)


  • Found in human embryos
  • Can develop into all types of adult cells (pluripotent)
  • More useful for medicine
  • Use comes with ethical implications
• ESCs are taken from embryos when they are 4-5 days old and then discarded
• Some people believe


  A human has a right to life from the moment of conception
• Continuous variation


  Characteristics controlled by many genes at different loci, where individuals in a population vary within a range
• Discontinuous variation


  Characteristics controlled by the expression of a single gene, where phenotypes can be grouped into distinct categories
• Monogenic


  Characteristics controlled by a single gene
• Monogenic characteristics


  • Blood type
• Polygenic


  Characteristics controlled by many genes at different loci
• Polygenic characteristics


  • Height
  • Weight
  • Skin colour
• Epigenetics


  Epigenetic modification involves the addition or removal of chemical 'tags' onto DNA or histone proteins
• Epigenetic modifications


  • Caused by environmental factors (such as diet, stress and smoking)
  • Can occur from as early as when we are in the womb
• Effect of epigenetic tags

  1. Addition or removal of epigenetic tags changes the structure of the chromosome

  2. Makes it either more or less accessible to RNA polymerase, transcription factors and other proteins involved in transcription

  3. More open structure = more accessible to RNA polymerase = gene switched on

  4. Less open structure = less accessible = transcription reduced = gene switched off
• Main types of epigenetic 'tags'


  • Methyl groups
  • Acetyl groups
• DNA methylation


  1. Methyl groups (-CH3) can be added directly onto the DNA

  2. Attach to CpG site (where a cytosine is found next to a guanine)

  3. Addition of methyl group makes DNA less accessible to proteins involved in transcription

  4. Gene is switched off (inactivated)
• Histone acetylation


  1. Chromosomes are made up of chromatin (DNA wrapped around histone proteins)

  2. Chromatin can be tightly wound (condensed) or more loosely wound (less condensed)

  3. More condensed chromatin = less accessible to proteins involved in transcription

  4. Addition of acetyl groups to histones causes chromatin to become less condensed, making it more accessible and activating the gene

  5. Removal of acetyl groups converts chromatin to more highly condensed form, which is less accessible and represses transcription of the gene