What Is Cell Differentiation? How Cells Become Specialised

Early in development, many cells are less specialised than the cells found in mature tissues. As development continues, signals inside and outside the cell affect which genes are active. Different patterns of gene activity lead cells to make different proteins, and those proteins help produce different structures and functions. A muscle cell makes large amounts of proteins involved in contraction, while a nerve cell develops structures suited to receiving and transmitting signals.

This is the key idea behind cell differentiation. A liver cell and a skin cell do not usually have completely different genomes. Instead, they read different sets of instructions from largely the same DNA. Some genes are active in many cell types because they support basic cell functions, while others are switched on mainly in particular tissues. Differentiation is therefore closely connected with gene regulation.

Cell shape often matches cell function after differentiation. Red blood cells lose their nucleus as they mature in mammals and develop a shape that helps them carry oxygen efficiently. Neurons can grow long extensions that carry signals over distance. Root hair cells in plants develop projections that increase surface area for absorbing water and minerals. Specialised structure is a visible result of deeper changes in gene activity and cell chemistry.

Stem cells are cells that can divide and can produce one or more specialised cell types. Some stem cells can form a very wide range of cell types, while others are more limited. During development, chemical signals help guide cells toward different fates. A cell's position in a tissue, the signals from neighbouring cells, and its earlier developmental history can all influence what it becomes.

Learning about cell differentiation also means understanding that the process is often gradual. A cell may pass through several intermediate stages before it becomes fully specialised. At each stage, some options become more likely and others become less available. Scientists study these steps by measuring gene activity, proteins, and cell behaviour to understand how tissues form and how development stays organised.

Differentiation continues to matter after early development. Adult tissues such as skin, blood, and the lining of the intestine constantly replace cells, using stem or progenitor cells that divide and then specialise. Other tissues replace cells much more slowly. Problems with differentiation can contribute to disease because cells may fail to mature normally or may grow in ways that ignore the usual controls. Plants also rely on differentiation. Cells produced in growing regions can become xylem cells for water transport, phloem cells for moving sugars, guard cells around stomata, or other specialised types. Comparing plants and animals shows that cell differentiation is a general developmental principle. Multicellular organisms need cells to divide work while remaining coordinated.

The claim that specialised cells keep essentially the same DNA was tested by experiment. In the mid twentieth century John Gurdon took the nucleus from a specialised intestinal cell of a tadpole and placed it into an egg cell whose own nucleus had been removed. Some of these eggs developed into tadpoles. The nucleus of a differentiated cell still held the instructions for a whole animal. In 1996 the same principle produced Dolly the sheep, cloned from an adult mammary cell.

In 2006 Shinya Yamanaka and colleagues showed that adding just four regulatory genes could push mature mouse skin cells back into a stem cell like state. These are called induced pluripotent stem cells, and the method was soon repeated with human cells. The result confirmed that differentiation is mostly about which genes are switched on, not about genes being lost. It also opened new research into growing specific cell types for studying disease.

When a skin cell divides, its daughters are still skin cells, not random cell types. Cells pass on a memory of their identity through chemical marks that sit on top of the DNA without changing its sequence. Small chemical groups called methyl groups can be attached to DNA, and the proteins that DNA is wrapped around can be tagged in different ways. These marks help keep some genes switched off and others accessible, and many are copied when a cell divides. The study of this kind of inheritance is called epigenetics.

A tortoiseshell cat is a visible example. A gene affecting orange or black fur sits on the X chromosome, and females have two X chromosomes. Early in development, each cell in a female embryo shuts down one X at random, and every descendant of that cell keeps the same one silenced. Skin patches grown from cells with one X active show one colour, and neighbouring patches show the other. The biologist Conrad Waddington pictured development as a ball rolling down a landscape of branching valleys, with each turn making the last one harder to reverse.

One way an embryo tells cells where they are is with a morphogen, a signalling substance that spreads from a source and forms a gradient, high near the source and lower further away. In 1969 the biologist Lewis Wolpert illustrated the idea with his French flag model. Imagine a row of cells next to a source. Cells that detect a high concentration become blue, those at a medium level become white and those at a low level become red. The same simple rule produces the same pattern every time, with each cell reading its position from the strength of the signal.

Real examples followed. In the fruit fly egg, the mother places messenger RNA for a protein called Bicoid at the front end, and the protein spreads backwards to form a gradient. Christiane Nüsslein-Volhard and colleagues showed in the late 1980s that the high concentration at the front helps specify the head, and embryos lacking Bicoid fail to develop proper head structures. In the developing wing of a chick, a small region at the rear edge releases a signal that helps set the identity of the digits. Graft an extra piece of that region onto the front edge, and a mirror-image duplicate set of digits forms.

Plants can reverse differentiation far more readily than animals. In the 1950s the botanist Frederick Steward grew whole carrot plants from small pieces of carrot root tissue cultured in a nutrient liquid, showing that ordinary specialised plant cells could produce every part of a new plant. Gardeners rely on the same flexibility when a cut stem grows roots. Plant scientists steer it with hormones. In tissue culture, a high ratio of auxin to cytokinin encourages roots, while a high ratio of cytokinin to auxin encourages shoots, a finding published by Folke Skoog and Carlos Miller in 1957.

Differentiation also matters in medicine. In acute promyelocytic leukaemia, a mutation fuses two genes so that developing white blood cells become stuck at an immature stage and pile up in the bone marrow. Researchers, notably in Shanghai in the 1980s, found that all-trans retinoic acid, a form of vitamin A, lets these cells resume maturing into neutrophils, which then die naturally. Combined with arsenic trioxide, this approach, called differentiation therapy, means most patients with this once rapidly fatal leukaemia now survive long term. It is the clearest example of treating a cancer by coaxing cells to finish specialising rather than killing them directly.

Cell differentiation is the process that turns less specialised cells into cells with particular structures and jobs. The DNA is usually similar across cell types, but patterns of gene activity are different. Follow the chain from signals to gene expression to proteins to cell structure, and you can see how one genome helps build many kinds of cells.