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Eukaryotic Cell Fate and

Differentiation

Cell and Microbiology 4LMS

Meggie Nikolić

m.nikolic@herts.ac.uk

C

Aims

• Understand the importance of stem cells in the formation

(development) and maintenance (adulthood) of tissues

• Understand the different types of stem cells
• Understand the principle of cell fate determination – what cells

can arise from the division of a stem cell

• Understand the principles of cell differentiation – how a newly

formed cell takes on its full function

The job of stem cells and precursor cells is not to

perform the specialised function of the

differentiated cells, but to generate cells that will

• Produce cells that

differentiate into the

tissue of our body (~

cell types in the body)

Characteristics:

• self-renewal
• can divide without limit (more in development; in adulthood they divide infrequently)
• not terminally differentiated
• daughter cells may become a stem cell or enter into terminal differentiation
• the cause of cancers

Stem cells

http://www.sciencemag.org/topic/stem-cells

Totipotent stem cells – most correct definition – stem cells that can

generate all three primary germ cell layers of the developing embryo – ectoderm, mesoderm and endoderm and form a whole organism. The fertilised egg is a totipotent stem cell, up to the 4 cell stage

After the 4 cell stage stem cells can generate all cell types, but cannot organise them into a body

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3991987/

Not totipotent

Embryonic stem cells = pluripotent

Divide in culture indefinitely (immortal)

If they are put back into an embryo, they will fully integrate and differentiate into any cell type

In culture they can be induced to differentiate into specific adult cell types

Cell harvested from the early embryo

Cell differentiation is a process of sequential changes that result in cell specificity (appearance and function)

Unipotent stem cells

Stem cells that generate only one cell type. Rare – not many good examples e.g. skin epithelium

Basal cells are the stem cells that divide to exclusively generate cells of the skin (epidermis)

Normal adult stem cells, e.g. skin

dermis

basal layer

dead cells

Terminal differentiation

stem cells

Modifying and using adult stem cells

Fibroblast cells can be isolated from the adult dermis (deeper layers of the skin) and genetically modified in the lab. to become pluripotent (so they divide to generate all types of adult cells)

They become pluripotent.

Garcia et al (2012) Front in Cell Neurosci. 6; 1-

Stem cells in therapy

A potential way to treat neurodegenerative diseases: Adult stem cells are removed from a patient, they are genetically modified to become neurones and then injected into the affected brain areas of the patient from which the skin stem cells were originally removed

Cell fate determination – how does it happen? One possible mechanism is dictated by how the stem cell divides Cell fate determinant protein is distributed throughout the stem, cell

Cell fate determinant protein is distributed on one side of the stem, cell

SYMMETRICAL ASYMMETRICAL http://www.md pi.com/2073- 8994/7/4/

e.g. two stem cells

e.g. one stem cell and one differentiated cell

Cell fate determination –

how does it happen?

A second possible mechanism is directed by the external environment (signalling)

If one of the daughter cells is exposed to a different environment which signals to it, it may differentiate into (become) a terminally differentiated cell

http://www.nature.com/articles/nri

A mammalian retinal neuron

A mammalian lymphocyte

• These two cells came from the same organism

and so have the same genomic DNA

• However, they have completely different appearance and different functions
• This is because of regulated gene expression leading to cell type-specific differentiation

https://www.ncbi.nlm.nih.gov/books/NBK26885/

Syracuse University Department of Physics

All living cells sense and respond to their environment by a set of

mechanisms known as cell signalling.

These mechanisms are part of a complex network of

communications that govern basic cellular activities and coordinate

the actions of cells.

Signalling