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Specialisation: how one genome becomes two hundred kinds of cell

Every cell in your body carries the same DNA, and yet a neurone a metre long and a red blood cell with no nucleus at all are both yours. The difference is not which genes are present but which are switched on — and once a cell has committed, the range of things it can still become narrows for good.

Before this Cell ultrastructure and the organelles · DNA, genes and the idea of transcription

Before you start

All your cells have the same DNA, so a neurone and a red blood cell must differ in the genes they carry — the neurone must have kept the nerve genes and lost the rest. It is a reasonable guess and it is wrong. With a few odd exceptions, every nucleated cell in your body holds a complete copy of the genome, haemoglobin genes and all. A cell in your retina carries the instructions for insulin and never uses them. What differs is not the library, it is which books are open.

What you should be able to do

Same genome, different cell

A fertilised egg divides into two, then four, then eight. The cells at that point are interchangeable, and each still carries the whole genome. By the time an adult exists there are somewhere over two hundred recognisably different cell types, still carrying the whole genome. Differentiation is the process that gets from the first state to the second.

It works by switching genes on and off. In any given cell only a fraction of the genome is being transcribed at any moment: the genes that cell needs. Which ones those are is set by signals the cell receives — from hormones, from growth factors, from its neighbours and from its position in the developing embryo — and once the pattern is established it tends to be maintained through subsequent divisions, so a liver cell's daughters are liver cells.

The consequences show up in the ultrastructure, which is where exam questions live. A cell that secretes protein for a living develops enormous quantities of rough ER and Golgi. A muscle fibre fills with protein filaments and mitochondria. A mature red blood cell goes further than any of them and loses its nucleus altogether, along with its mitochondria, leaving room for about 270 million molecules of haemoglobin — and no way of dividing or repairing itself, which is why it lasts only about 120 days.

A sperm cell makes the same trade in a different direction: almost no cytoplasm, a head packed with a haploid nucleus, a cap of digestive enzymes called the acrosome to get through the egg's outer layers, and a mid-piece stuffed with mitochondria to power the tail. Every one of those features is a gene expression decision made visible.

Differentiation
The process by which a cell develops the structures and characteristics needed to carry out a particular function, through some genes being expressed and others not.
Specialised cell
A cell whose structure is adapted to one particular function.

How much a stem cell can still become

A stem cell is an undifferentiated cell that can keep dividing and can develop into other cell types. Both halves matter, and the second is what keeps the first possible: stem cells divide in a way that replaces themselves as fast as they are spent, so the supply is not used up. The textbook picture is a single division giving one daughter that differentiates and one that stays a stem cell, and that does happen. It is not the only arrangement. In plenty of tissues both daughters differentiate, or both stay, and the balance is struck across the population rather than inside every division.

Stem cells are classified by how wide a range of cells they can still produce, and the range narrows as development proceeds. The three terms are examinable and the distinction between the first two is a single specific thing.

The only difference between the top two rows is the placenta. That one detail is what most mark schemes are looking for.
Totipotent
Able to develop into any cell type in the organism and into the extra-embryonic tissues such as the placenta. Found in the zygote and the cells of the first few divisions.
Pluripotent
Able to develop into any cell type in the body, but not into the placenta. Found in embryonic stem cells in the blastocyst.
Multipotent
Able to develop into a limited range of cell types. Found in adult stem cells, such as those in bone marrow which produce the blood cells.

Bone marrow is the standard multipotent example and a good one because the limits are visible. A haematopoietic stem cell in the marrow can produce red blood cells, all the kinds of white blood cell and platelets — but nothing else. It cannot make a neurone, however useful that might be, because the genes a neurone would need are packed away and nothing the marrow does in the ordinary course of events opens them again.

The narrowing is why stem cell medicine is hard and why it matters. Pluripotent cells could in principle replace almost anything, but obtaining them from embryos raises ethical objections that have shaped the law in most countries. Induced pluripotent stem cells offer a way round: adult cells, usually from skin, are treated with specific transcription factors that switch previously silent genes back on, and the cells revert to a pluripotent state. Because they come from the patient, tissue made from them is not rejected. Those cells are also the cleanest demonstration that differentiation is very hard to reverse rather than genuinely irreversible: the genes were never thrown away, only shut down, and with the right transcription factors applied deliberately they open again.

Cells, tissues, organs, systems

Multicellular organisms are organised in levels, and each level is built from the one below it. The definitions look obvious until you have to write one down under pressure.

One chain in an animal and one in a plant. Follow either from left to right and the definitions define themselves.
Tissue
A group of similar cells working together to perform a particular function.
Organ
A structure made of several different tissues working together to perform a particular function.
Organ system
A group of organs working together to perform an overall life function.

The line that gets blurred is between tissue and organ, so use the number of tissue types to decide. Ciliated epithelium is one kind of cell doing one job, so it is a tissue. The trachea contains that epithelium plus cartilage, smooth muscle, connective tissue and blood vessels, all working together to keep an airway open and clean, so it is an organ. The gas exchange system is the trachea plus the bronchi, bronchioles, lungs and diaphragm.

Two epithelia are worth knowing precisely, because they are the standard structure-and-function examples.

Squamous epithelium is a single layer of very flat cells, so thin that the nucleus makes a visible bulge. It lines the alveoli and forms the walls of capillaries, and the reason is diffusion distance: a thin barrier means a short path for oxygen and carbon dioxide, and a steep concentration gradient is easier to maintain across it.

Ciliated epithelium is a layer of column-shaped cells each carrying hundreds of cilia that beat in a coordinated wave. It lines the trachea, bronchi and oviduct. In the airway it works with the goblet cells scattered among it: the goblet cells secrete mucus that traps dust and bacteria, and the cilia sweep the loaded mucus up towards the throat to be swallowed. Damage the cilia — smoking does this — and the mucus stays where it is, which is what a smoker's cough is trying to fix.

Two plant tissues worth knowing properly

Plants are organised the same way. Xylem and phloem are tissues; a leaf, a root and a stem are organs; together they make a transport system. Both tissues are built from cells that gave something up, and in each case what was given up is the interesting part.

Two solutions to moving fluid through a plant. One tube dies and empties itself; the other stays alive and keeps a neighbour to run it.

Xylem carries water and dissolved mineral ions from root to leaf, and in a transpiring plant the flow runs one way: upwards. A xylem vessel is a file of cells whose end walls have broken down completely, leaving one continuous hollow tube, sometimes metres long. The cells die in the process: the cytoplasm, nucleus and organelles are gone, so there is nothing to obstruct the flow. The side walls are thickened with lignin, laid down in rings and spirals, which waterproofs them and stops the tube collapsing inwards when the water inside is under tension. Small unlignified gaps called pits let water pass sideways into neighbouring cells.

Phloem carries sucrose and amino acids from where they are made or stored to wherever they are needed — up the plant in spring, down it in summer, either way at any time. That flexibility rules out the xylem solution. A sieve tube element keeps its plasma membrane and a thin layer of cytoplasm, but loses its nucleus, ribosomes and most other organelles to clear a path down the middle. Its end walls survive as sieve plates, perforated with pores that the contents flow through.

A cell with no nucleus and no ribosomes cannot maintain itself, so it does not try. Each sieve tube element has a companion cell alongside it, connected through plasmodesmata, with a nucleus, dense cytoplasm and a great many mitochondria. It makes the proteins the sieve tube needs and supplies the ATP for actively loading sucrose into the tube. Take the companion cell away and the sieve tube stops working, because there is nothing left to replace its proteins or to pay for the loading, and it has no means of doing either itself.

Xylem vesselPhloem sieve tube
Living?No — dead and emptyYes, but without a nucleus
End wallsBroken down completelyRemain as perforated sieve plates
WallThickened with ligninCellulose, unthickened
TransportsWater and mineral ionsSucrose and amino acids
DirectionUpwards onlyUp or down
Partner cellNoneCompanion cell, rich in mitochondria

TRY IT — Reading a function off a structure

A student examines a stained section of a plant stem and finds a tube with no cell contents at all, whose walls carry thick spiral bands that stain red for lignin. Identify the tissue and explain three ways its structure suits its function.

Check your answer

It is xylem — specifically a xylem vessel.

The absence of cell contents means the tube is hollow from end to end, with no cytoplasm, nucleus or end walls in the way, so water moves through it with very little resistance and the column stays unbroken.

The lignin waterproofs the wall, so water is not lost sideways into the surrounding cells as it travels, and it also stiffens the tube so it does not collapse under the tension produced when water is pulled up from the leaves.

The spiral rather than continuous arrangement of the lignin is a third mark if you spot it: it leaves the wall able to stretch as the stem grows, and leaves unlignified pits through which water can move sideways where it is needed.

The same lignin gives the stem much of its mechanical strength, which is why wood is mostly old xylem.

In the exam

Check yourself

Cells lining the trachea and cells lining the alveoli both come from the same fertilised egg and carry the same DNA, yet one is a tall cell covered in cilia and the other is so flat it is barely visible in section. Explain how this difference arises and why each shape suits where the cell is.

Answer

Both cells hold a complete copy of the genome. The difference comes from gene expression: in each cell only the genes needed for that cell type are transcribed, and the rest stay switched off. Which genes those are was determined during development by the signals each cell received, including its position in the growing airway, and the pattern is then inherited by its daughter cells.

The ciliated cell in the trachea has expressed the genes for the proteins that build cilia and for the mitochondria that power them. Its job is to keep the airway clean: goblet cells among the epithelium secrete mucus that traps dust and bacteria, and the coordinated beating of the cilia sweeps that mucus up to the throat, away from the lungs.

The squamous cell in the alveolus has done the opposite and become as thin as a cell can be. Its job is to be got through. Oxygen and carbon dioxide diffuse across the alveolar wall, and rate of diffusion falls as the distance rises, so a wall one flattened cell thick keeps the path as short as possible.

Neither cell could do the other's job, and neither can change into the other, because differentiation is very hard to reverse once the pattern of expression is fixed.

Questions

Written to the command words the boards use. Try them on paper before opening a scheme: the marks go to points made, not to length.

Question 14 marks

A stem cell in the bone marrow and a mature sperm cell carry exactly the same DNA. Explain how the two cells come to have such different structures.

Mark scheme
  1. B1 every cell holds a complete copy of the genome, so the genes present in the two cells are the same
  2. B1 only a fraction of those genes is transcribed in any one cell, so different proteins are made and different structures develop
  3. B1 which genes are expressed is set by the signals a cell receives, such as hormones, growth factors, its neighbours and its position in the embryo
  4. B1 once established the pattern of expression is maintained through subsequent divisions, so a cell's daughters stay the same type

Question 24 marks

A phloem sieve tube element has lost its nucleus and almost all of its organelles, yet it is still alive. Explain how this suits it to its function, and explain why it cannot work without a companion cell.

Mark scheme
  1. B1 losing the nucleus and most organelles clears the centre of the tube, so sap flows through with little obstruction
  2. B1 the end walls survive as sieve plates perforated with pores, through which the contents pass from one element to the next
  3. B1 with no nucleus and no ribosomes the element cannot make its own proteins, so the companion cell makes them and passes them through plasmodesmata
  4. B1 the companion cell has dense cytoplasm and many mitochondria, and supplies the ATP for loading sucrose actively into the sieve tube

Question 33 marks

Compare a totipotent cell, a pluripotent cell and a multipotent cell, giving one place each type is found.

Mark scheme
  1. B1 a totipotent cell can produce any cell type in the organism and the extra-embryonic tissues such as the placenta, and is found in the zygote and the first few divisions
  2. B1 a pluripotent cell can produce any cell type in the body but not the placenta, and is found in the embryonic stem cells of the blastocyst
  3. B1 a multipotent cell can produce only a limited range of cell types, and is found in adult tissues such as bone marrow

Question 43 marks

Long-term smokers secrete more mucus than usual and the cilia on their airway epithelium are damaged. Suggest why such a smoker develops a persistent cough and gets more chest infections.

Mark scheme
  1. B1 cilia normally beat in a coordinated wave that sweeps mucus up towards the throat to be swallowed
  2. B1 with the cilia damaged the mucus is not moved, so it collects in the airways and coughing is the only way left to shift it
  3. B1 that mucus holds trapped dust and bacteria, which now stay in the airway and can multiply there, so infections are more likely

Question 52 marks

State what is meant by a tissue, and state what is meant by an organ.

Mark scheme
  1. B1 a tissue is a group of similar cells working together to perform a particular function
  2. B1 an organ is several different tissues working together to perform a particular function

Worth remembering

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