L21, 22 & 23: Stem Cells

Question 1

What are the three characteristics that define a stem cell?

Answer 1

Cell that can:

• Proliferate
• Differentiate
• Self-renew

Question 2

Define unipotent, totipotent, pluripotent and multipotent.

Answer 2

Unipotent = can only become one type of cell

Totipotent = can produce any type of cell

Pluripotent = can produce all somatic cell types, but cannot become extraembryonic tissues.

Multipotent = can produce some somatic cells time (e.g. cells from ectoderm can produce ectoderm derivates, but not mesoderm derivatives.

Question 4

What signals tell a cell to go down a particular pathway?

Answer 4

• Cytokines, growth actors
• Transducers (transcription factors)
• Asymmetri cell division (cell contents are asymmetrically distributed during division. Produces different cells with different amount/type of signals.

Question 5

How do tissues regenerate without the use of stem cells?

Answer 5

THey have differentiated cells that can re-enter mitosis, ie. leave G0 back to G1.

E.g. Hepatocytes. Cells can re-grow 70% removal of liver mass.

Question 6

Why are most mature cells terminally differentiated?

Answer 6

Imagine if neurons and cardiac cells were capable of re-entering S phase and dividng. They would lose their function while in mitosis - not good!

Thus, cell replacement must come from other cells.

Most adult tissues contain tissue-specific stem cells in reversinble G0 (quiescent)

Question 7

What are the problems with repeated cell division?

Answer 7

• Telomere shortening
• Mutation accumulation

Question 8

What is a stem cell niche?

Answer 8

A stem-cell niche is an area of a tissue that provides a specific microenvironment, in which stem cells are present in an undifferentiated and self-renewable state. Cells of the stem-cell niche interact with the stem cells to maintain them or promote their differentiation.

Question 9

What is plasticity?

Answer 9

The ability to become another cell type.

Bipotential = low plasticity

Multipotential = high plasticity

Plasticity is governed by the stem cell niche, which produces different signals to control gene expression.

Question 10

What are the common signalling pathways for stemcells?

Answer 10

• TGF-beta - Induces quiescnece, inhibits proliferation
• Hh (Hedgehog) - Induces proliferation
• Wnt (wingless integration) - Induces specific cell fates, stages of diff
• Notch - Inhibits stem cell proliferation, differentiation and self-renewal

Question 11

What is the process of stem cell activation?

Answer 11

Stimuli causes the cell to exit G0 (quiescence).

They undergo asymmetric division to produce one cell that has stem cell properties and another transient amplifying cell.

Question 12

How does Notch signalling work?

Answer 12

Numb protein inhibits notch.

Numb protein is asymmetrically distributed in stem cell mitoses (asymmetric division).

• Numb protein is LOW in true SCs, allowing notch not to be activated and keeping the SC in quiescence
• Numb protein is HIGH in differentiate cells (Notch-), allowing it to REPRESS notch and let the SC differentiate.

Question 13

Describe the location, purpose and what signals are involved in satellite cells.

Answer 13

Location: Skeletal muscle

Function: Make skeletal muscle

Guided by transcription factors:

• Pax7 activates
• MyoD proliferates
• Myogenin diverges

Question 14

Describe the location, purpose and signals involved in haemotopoietic stem cells.

Answer 14

Location: Bone marrow

Purpose: Makes all blood cell types - multipotent

Signals involved: Erythropoietin - released by kidneys in response to hypoxia.

Question 15

Why are stem cells useful in research>

Answer 15

Their properties of self-renewal and differentiate means they can be maniupulated in vitro, excellent for studying development and disease.

Question 16

Describe the process of somatic cell nuclear transfer (SCNT)?

Answer 16

Donor nucleus is put into an egg cell that had its nucleus removed. This forms a fused cell that is a fully functional embryo.

The embryo was put into a foster mother, and produced Dolly.

This demostrated that the genome in every cell is the same, and that nuclear gene activity is determined by TFs and proteins in egg cytoplasm.

Question 17

What are the differences between embryonic stem cells and adult stem cells?

Answer 17

Embryonic stem cells are formed in early embryo, and are pluripoent - can develop into all types of cells.

Adult stem cells are present in individual tissues, and are multipotent.

Question 18

What are induced pluripotent stem cells (iPSCs)?

Name three uses.

Answer 18

Have the same qualities as embryonic stem cells, but are produced in a lab.

1. Can be used therapeutically, through gene correction to make healthy specialised cells that are re-introduced to patients
2. Can be used to study disease, test new drugs
3. Can use patient-derived iPSC cells in transplants to avoid rejection.

Question 19

What are organoids, and what is their use?

Answer 19

There is a big difference between the way cells behave in culture compared to how they behave in complex organs.

Organoids aim to mimic the complexity on an organ. They are formed from small balls of pluripotent cells that mimic organogenesis.

Question 20

What are some challenges to cell replacement therapy?

Answer 20

1. Rejection (stem cells from unrelated donor)
2. Tumour development (proliferate capacity of ESCs means there is a higher chance of tumours being formed)
3. Ethical issues (with creation of blastocysts)
4. Knowledge (lack knowledge in developmental signalling molecules)

Question 21

What are two examples of stem cell replacement therapy today?

Answer 21

Haematopoietic stem cell transplants - Infusion of HSCs isolated from bone marrow given to patient.

Keratinocyte grafts - Keratinocytes can be isolated from healthy skin and used to repair damaged skin, usually in burns.

Sourced from hair follicles, they can be transplanted as sheets, or as a spray.