Stem Cells and Differentiation

All the specialised cells of a multicellular organism arise from unspecialised precursor cells through the process of differentiation. Stem cells are undifferentiated cells that retain the ability to divide and give rise to specialised cell types. Understanding stem cell biology, the different categories of stem cell potency, and the ethical considerations surrounding their use is required for AQA A-Level Biology (specification 3.2.2).

Key Definition: A stem cell is an undifferentiated cell that is capable of self-renewal (dividing to produce more stem cells) and differentiation (giving rise to one or more specialised cell types). Differentiation is the process by which a cell becomes specialised for a particular function through the expression of specific genes.

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How Differentiation Occurs

All cells in a multicellular organism contain the same DNA (the same genome) — they are genetically identical (they all arose from the same zygote by mitosis). However, different cells express different genes.

The Mechanism of Differentiation

• During differentiation, specific genes are switched on (expressed) and others are switched off (silenced).
• The genes that are expressed determine which proteins are made, which in turn determines the cell's structure and function.
• Gene expression is controlled by transcription factors — proteins that bind to specific regions of DNA and either activate or repress transcription of target genes.
• Epigenetic modifications also play a role: chemical changes to DNA (e.g., methylation of cytosine bases) or to histone proteins (e.g., acetylation, methylation) can alter gene expression without changing the DNA sequence. These modifications can be inherited during cell division.

Example: A red blood cell precursor (erythroblast) expresses the gene for haemoglobin at very high levels, while a neurone does not express this gene but instead expresses genes for neurotransmitter receptors and ion channels. Both cells contain the haemoglobin gene, but it is only active in the erythroblast.

Irreversibility of Differentiation (in Most Cases)

• In most animal cells, differentiation is effectively irreversible — once a cell has become specialised, it typically cannot revert to an unspecialised state under normal conditions.
• In plants, differentiation is often reversible — many differentiated plant cells can dedifferentiate and form new tissues or even entire organisms (totipotency is retained). This is the basis of cloning plants from cuttings and tissue culture.

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Categories of Stem Cell Potency

Stem cells are classified according to their potency — the range of cell types they can give rise to.

Potency	Definition	Examples
Totipotent	Can differentiate into any cell type, including extraembryonic tissues (e.g., placenta)	Zygote and cells of the early embryo (up to about the 8–16 cell stage, the morula)
Pluripotent	Can differentiate into any cell type of the body (all three germ layers: ectoderm, mesoderm, endoderm) but not extraembryonic tissues	Cells of the inner cell mass of the blastocyst (embryonic stem cells)
Multipotent	Can differentiate into a limited range of cell types within a particular tissue or lineage	Haematopoietic stem cells in bone marrow (give rise to all blood cell types: red blood cells, white blood cells, platelets). Neural stem cells (give rise to neurones and glial cells)
Unipotent	Can differentiate into only one cell type	Epithelial stem cells at the base of villi in the small intestine (produce only epithelial cells). Muscle satellite cells (produce only muscle cells)

Exam Tip: You must be able to define each level of potency precisely. 'Totipotent' and 'pluripotent' are often confused — the key difference is that only totipotent cells can form the placenta and other extraembryonic tissues.

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Embryonic Stem Cells (ESCs)

Source

• Derived from the inner cell mass (ICM) of the blastocyst — an early-stage embryo (approximately 5–7 days after fertilisation in humans).
• The blastocyst consists of an outer layer of cells (trophoblast, which forms the placenta) and the ICM (which forms the embryo).

Properties

• Pluripotent: can differentiate into virtually any cell type.
• Can be grown in culture for extended periods while maintaining their undifferentiated state (given the correct growth factors).
• Can be directed to differentiate into specific cell types by exposure to particular combinations of growth factors and signalling molecules.

Potential Therapeutic Uses

• Regenerative medicine: replacing damaged or diseased cells and tissues. Examples include:
  • Growing new insulin-producing beta cells for type 1 diabetes.
  • Producing dopamine-secreting neurones for Parkinson's disease.
  • Generating cardiomyocytes (heart muscle cells) to repair damage after myocardial infarction.
  • Growing new retinal cells for macular degeneration.
• Drug testing: differentiated cells can be used to test new drugs for efficacy and toxicity in vitro, reducing the need for animal testing.
• Disease modelling: ESCs from embryos with genetic diseases can be used to study disease mechanisms.

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Adult Stem Cells