Cell specialisation and biological organisation

Same genome, different cell

A fertilised egg divides into two, then four, then eight. The cells at that point are interchangeable, and each carries the whole genome. An adult body contains over two hundred recognisably different cell types, and most nucleated somatic cells still contain the same genome. Differentiation is the process leading 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. Once the pattern is established it tends to be maintained through subsequent divisions, so a liver cell's daughters are liver cells.

The consequences appear in the ultrastructure. A cell specialised for protein secretion develops extensive 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 packed with mitochondria to supply ATP for the tail. Each of those features is the visible result of a particular pattern of gene expression.

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 first is what keeps the second 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 the range of cell types they can still produce, and that range narrows as development proceeds. The three terms below are examinable, and totipotency differs from pluripotency in one respect only.

Describe the drawing

Three stacked cards, one for each kind of stem cell, joined by downward arrows. The top card is totipotent, found in the zygote and its first few divisions, able to make every cell type and the placenta. The middle card is pluripotent, found in embryonic stem cells of the blastocyst, able to make every cell type in the body but not the placenta. The bottom card is multipotent, found in adult stem cells such as those in bone marrow, able to make only a limited range. A coloured bar on each card shrinks from top to bottom.

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 produce a neurone, because the genes a neurone requires remain unexpressed and are not reactivated by any signal the marrow normally supplies.

This narrowing is the central difficulty in stem-cell medicine. Pluripotent cells could in principle replace almost any tissue, 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 carries a much lower risk of rejection, though not zero: reprogramming and time in culture can alter the cells enough to provoke an immune response. Induced pluripotent cells also demonstrate that differentiation is difficult to reverse rather than genuinely irreversible: the genes are retained rather than lost, and specific transcription factors can restore their expression.

Cell theory

Cell theory is the statement that ties the rest of this unit together. It has three parts. All living organisms are made of one or more cells. The cell is the fundamental unit of structure, function and organisation in every living organism. New cells arise only from the division of existing cells.

The first two parts were set out by Matthias Schleiden for plants in 1838 and Theodor Schwann for animals in 1839, after improved light microscopes showed the same basic unit in plant tissues and in animal tissues such as cartilage. The third was established in the 1850s and is summed up in the phrase Rudolf Virchow made famous, omnis cellula e cellula, every cell from a cell. It ended the idea that cells could form spontaneously from non-living material, and it is why growth and repair are explained by cell division.

Cell theory is called a unifying concept because it applies to every organism, from a single bacterium to an oak tree, and because so much of biology can be explained at the level of the cell. Respiration, protein synthesis and the replication of DNA happen inside cells. A tissue is a group of similar cells, an organ a group of tissues, and the properties of each level depend on the cells it is built from. Disease, too, is understood as a failure of cells, which was Virchow's own application of the theory.

A few structures look like exceptions and are not. A striated muscle fibre contains many nuclei in one long cell, because it forms when many precursor cells fuse. A fungal hypha is often not divided into separate cells. A mature red blood cell has no nucleus, and a xylem vessel element is dead. Each of these is still made by cells and from cells, so the theory holds; what they show is that a cell can be modified a long way from the textbook diagram. Viruses are the test case in the other direction. A virus is not made of cells and cannot carry out any function outside one, which is the reason it is classed as non-living.

Cell theory

The unifying concept that all living organisms are made of one or more cells, that the cell is the fundamental unit of structure, function and organisation, and that new cells arise only from existing ones.

Cells, tissues, organs, systems

Multicellular organisms are organised in levels, and each level is built from the one below it. Learn the definitions in a form that can be written out precisely.

Describe the drawing

Four stages left to right joined by arrows, headed cell, tissue, organ and organ system. Above the labels are simple drawings: one ciliated cell, then four of them side by side as an epithelium, then a ringed tube, then that tube with two lungs attached. Beneath each stage two example chains are printed, an animal one reading ciliated epithelial cell, ciliated epithelium, trachea, gas exchange system, and a plant one reading xylem vessel element, xylem tissue, root, transport system.

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 layer of similar cells doing one job, so it is a tissue. (The definition says similar cells rather than identical ones, which matters here: the goblet cells that make the mucus sit in the same layer.) 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 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 the shorter the path, the faster they diffuse 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. Smoking damages the cilia, so mucus is no longer cleared from the airway and accumulates, and coughing becomes the only means of removing it.

Epithelia are not the only kind of animal tissue, and cartilage is the connective tissue worth knowing as the contrast. In an epithelium the cells sit shoulder to shoulder and the tissue is nearly all cell. Cartilage is nearly all matrix: its cells, called chondrocytes, sit isolated in small spaces named lacunae, surrounded by the firm, elastic extracellular material of collagen fibres and glycoproteins that they secreted around themselves. The matrix is the tissue's working part, smooth enough to glide and stiff enough to hold a shape while still absorbing compression.

That is why cartilage turns up where the body needs a surface or a support that must not collapse: capping the ends of bones at joints, shaping the ear and the nose, and stiffening the wall of the trachea, where the C-shaped rings of it are one of the several tissues that make the trachea an organ rather than a single tissue. Cartilage contains no blood vessels, so its chondrocytes are supplied by diffusion through the matrix alone, and that slow supply is why a damaged cartilage surface repairs so poorly compared with the bone beneath it.

Cartilage

A connective tissue in which chondrocytes, lying in lacunae, are surrounded by a firm extracellular matrix of collagen that they secrete; it has no blood vessels and supports structures such as the trachea, joints, ear and nose.

Muscle is the third kind of animal tissue to know, after epithelium and cartilage. Its cells are packed with protein filaments that slide past one another, so each cell can shorten. In the airway wall it is smooth muscle: spindle-shaped cells that contract together, without conscious control, to narrow the lumen.

Xylem and phloem

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. In both tissues the conducting cells lose organelles as they differentiate, and which organelles are lost determines how each tissue works.

Describe the drawing

Two plant transport tubes drawn side by side in longitudinal section. On the left a xylem vessel: a wide open tube with no end walls anywhere along it, walls thickened with rings of lignin, nothing at all inside, and a single arrow running straight up it. On the right a phloem sieve tube: a narrower tube crossed at intervals by perforated sieve plates, with a companion cell alongside containing a nucleus and several mitochondria, and a double-headed arrow showing that sap can travel either way.

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 synthesise its own proteins. Each sieve tube element therefore 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.

The two tissues contrast at every row of that table, but they share an origin. In a stem, xylem vessels and sieve tubes are produced by the same dividing population of unspecialised cells.

That population is a meristem, the plant equivalent of a multipotent animal stem-cell population. A meristem is a tissue of small, thin-walled, unspecialised cells that go on dividing while the cells around them have stopped, and the vascular tissue of a stem comes from two of them in succession. In a young shoot the strands of procambium running back from the apical meristem divide and their products differentiate in two directions: the ones left on the inner face of the strand thicken their walls with lignin, break down their end walls, lose their contents and become the first xylem vessels, while the ones left on the outer face keep their plasma membrane and cytoplasm, perforate their end walls into sieve plates and become the first sieve tubes. The two daughters did not differ at the moment of division. They differed in position, and therefore in the signals each received, which is the same mechanism of differentiation described for animal cells above.

In a dicot stem that goes on to thicken, a strip of that meristem is kept for life as the vascular cambium, the layer of dividing cells the plan-diagram convention shows between the xylem and the phloem of every bundle. It divides the way a stem cell divides: one daughter stays cambium, so the supply is never spent, and the other differentiates according to which side of the cambium it was left on. Inwards it becomes secondary xylem, outwards secondary phloem. Years of that adds up, and the result is visible from outside the plant: wood is accumulated secondary xylem, and the living inner layer of bark is secondary phloem. Both were made by the same cells.

The cambium can be classified in the same terms as an animal stem cell. A haematopoietic stem cell is multipotent and can make any blood cell and nothing else; the cambium is multipotent in the same sense, restricted to the vascular fates and their supporting parenchyma. The difference is that an animal keeps very few such populations and keeps them hidden, whereas a plant keeps meristems at every growing tip and around every thickening stem, for as long as it lives. That is why a cutting can grow a whole new plant and a severed finger cannot.

Meristem

A plant tissue of unspecialised cells that continue to divide, from which specialised cells such as xylem vessels and sieve tube elements differentiate.

Vascular cambium

The meristem layer lying between the xylem and the phloem of a vascular bundle, whose divisions add secondary xylem on its inner side and secondary phloem on its outer side.