Mechanisms of Disease I: Cell Growth and Differentiation

Question 1

What’s the difference between cell growth and cell differentiation?

Answer 1

Cell growth and differentiation are the basic mechanisms responsible for turning a zygote into a mature multicellular organism
Cell growth = a bigger organism, more cells
Differentiation = cells become complex, (usually) an end to growth
Cell growth precedes differentiation, but with some overlap

Question 2

What categories can pathological cell growth and differentiation fall into?

Answer 2

Developmental conditions
- Can be related to cell growth or differentiation (or both)
- E.g. Neural tube defects like spina bifida
Neoplasia (and metaplasia which is the transformation of one cell type into a new one)
- E.g. cancer, tumours
Others, e.g. cardiac hypertrophy

Question 3

What are the two forms of cell growth?

Answer 3

Two main forms:

- hypertrophy (bigger cells)
- hyperplasia (more cells)- most common form of cell growth in humans

Question 4

What is hypertrophy?

Answer 4

Hypertrophy is simply cells growing bigger
- More proteins, more membrane etc. etc.
- Elevated protein synthesis is a big driver of increased cell size
The heart is a classic example

Question 5

What is hyperplasia?

Answer 5

Hyperplasia – more cells – is caused by cell division, or proliferation

Question 6

What governs cell growth and differentiation?

Answer 6

Cell growth and differentiation are governed by the integration of multiple signals:
- intra- and extracellular signals (checks on cellular physiology, growth and inhibitory factors, cell adhesion etc.)
Signals converge on the promoters of key genes
- Promoters act as “co-incidence detectors”
Express gene YES/NO? How much?

Question 7

What are the three classes of extracellular signals?

Answer 7

Three broad classes:

- Paracrine: produced locally to stimulate proliferation of a different cell type that has the appropriate cell surface receptor
- Autocrine: produced by a cell that also expresses the appropriate cell surface receptor
- Endocrine: like conventional hormones, released systemically for distant effects

Question 8

What are the different kinds of extracellular signals involved in cell growth and differentiation?

Answer 8

Proteins that:
Stimulate proliferation and promote survival
- Mitogens
- e.g. Growth factors and interleukins (EGF, FGF, NGF, PDGF, IGF1, IL2, IL4)
Induce differentiation and inhibit proliferation, e.g. TGFb
Can do either, e.g. Wnt ligands
Induce apoptosis, e.g. TNFα and other members of the TNF family