Development, stem cells and gene regulation

What you’ll learn

• Distinguish totipotent, pluripotent and specialised cells.
• Explain differential gene expression, alternative splicing and epigenetic regulation.
• Compare multiple alleles, polygenic inheritance and environmental effects.

Understand the idea

Early divisions of a mammalian zygote produce a solid ball of cells called a morula and then a blastocyst with a cavity and an inner cell mass. Totipotent cells can generate all the cell types needed for a whole organism, including extraembryonic tissues. Pluripotent cells can form many body cell types but cannot independently produce all those supporting tissues. Stem cells can self-renew and differentiate; specialised cells perform particular functions. Potential therapies must be evaluated for appropriate differentiation, tumour risk, immune compatibility, effectiveness and ethical concerns about the cell source.

Most nucleated body cells contain essentially the same genome, yet express different sets of genes. Transcription of particular genes produces mRNA and then proteins that establish cell structure and activity. Alternative splicing can include different combinations of exons in mature mRNA, allowing one gene to produce different protein products. Epigenetic changes regulate gene activity without changing the DNA base sequence: DNA methylation is often associated with reduced transcription, while histone modifications can make chromatin more or less accessible. Some marks are maintained through mitotic division; this does not mean all acquired changes are inherited between generations.

Phenotype depends on genotype and environment. A gene may have more than two alleles in a population, although a diploid individual normally carries at most two at that locus. ABO blood groups illustrate this: $I^A$ and $I^B$ are codominant with each other and both are dominant to $i$. Thus $I^A I^B$ gives group AB and $ii$ gives group O. Polygenic characteristics are affected by several genes, often producing a range of values; environmental effects can broaden that continuous variation further. Human height, for example, reflects many genetic influences as well as nutrition and other developmental conditions.

Worked example

A liver cell and a nerve cell from the same person contain the same gene for a liver enzyme, but only the liver cell produces much of that enzyme. Explain the difference without proposing that the nerve cell has deleted the gene.

1. The two cells can retain the same DNA sequence at the enzyme gene.
2. Different regulatory signals and chromatin states can make transcription active in the liver cell and low or absent in the nerve cell.
3. The liver cell therefore has more corresponding mRNA and synthesises more enzyme, contributing to its specialised function.

Answer: The difference is selective gene expression, rather than a necessary difference in gene presence.