L6 The stem cell niche Flashcards

1
Q

Where are adult stem cells generally found in?

A

They are found in special micro environments called niches.

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2
Q

What type of cells does the embryo start off as?

A

A clump of totipotent stem cells (embryonic stem cells).

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3
Q

What are the different distinct stem cells in the adult?

A
  • Mesenchymal stem cells: Bone cells (osteoblasts), cartilage cells (chondrocytes) and fat cells (adipocytes)
  • Blood stem cells: red blood cells, platelets and white blood cells
  • Satellite stem cells: muscle
  • Germ cells: oocytes and sperm
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4
Q

How are the stem cells said to set aside in the developing embryo for adult use?

A

It is thought that there are special mechanisms in the developing embryo that set aside these cells for use in the adult.

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5
Q

How long would RBC, white blood cells, skin, colon, sperm and brain cells last for?

A

Red blood cells live for about four months

White blood cells more than a year

Skin cells two or three weeks

Colon cells about four days

Sperm cells about three days

Many brain cells can last an entire lifetime

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6
Q

Why is stem cell maintenance so important?

A

Stem cell maintenance is a tightly regulated process that ensures the long-term survival and functionality of these essential cells. By understanding the underlying mechanisms, we can potentially harness their therapeutic potential for regenerative medicine and age-related diseases.

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7
Q

What is stem cell maintenance?

A

Stem cell maintenance is the process by which stem cells preserve their unique properties by dividing and differentiating

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8
Q

What is the main aim of stem cell maintenance?

A

It’s main role is to maintain the same stem cell population

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9
Q

Explain the division of stem cells

A
  1. There are three sorts of division.
  2. division rates must be balanced so as to keep stem cell population constant
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10
Q

Does the epidermis needs to be continually renewed?

A

Yes

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11
Q

What are the three main layers of the skin?

A

Epidermis - Made up of keratinocytes
Dermis - Contains fibroblast and blood vessels.
Subcutis.

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12
Q

What stimulates keratinocyte proliferation?

A

Signals from the dermis and basement membrane stimulate keratinocyte proliferation.

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13
Q

Which layer of the skin contains the stem cells?

A

The basal layer contains the stem cells that proliferate.

The daughter cells are pushed progessively to the skin surface where they die

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14
Q

What is produced that provides strength to the skin and moves towards the surface

A

Cells produce high levels of the fibrous protein keratin that provides strength to the skin

Cells produce different keratins as they move towards the surface.

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15
Q

What inhibits differentiation and maintains the stem cell population?

A

Wnt signals from the dermis inhibits differentiation (maintains stem cell population).

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16
Q

What are wnt signals?

A

Wnt signals represent a complex and highly conserved group of signal transduction pathways that are fundamental to a wide range of biological processes

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17
Q

What is the role of integrin?

A

Integrins (adhesion molecules) hold cells to the basement membrane (maintains stem cell population).

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18
Q

What inhibits integrins?

A

Notch signals in maturing keratinocytes inhibit integrins.

19
Q

What inhibits Notch activity?

A

EGF inhibits notch

20
Q

How does Egf maintain stem cell maintenance?

A

Egf inhibits Notch activity, which inhibits integrins, which are responsible for holding cells to the basement membrane which ultimately decreases stem cell population

21
Q

What is the stem cell niche in the epidermis?

A

The basal layer of the epidermis is a stem cell niche

22
Q

What is the stem cell niche called in the hair follicle

A

There is another stem cell niche in the hair follicle called the bulge.

23
Q

What forms the follicles?

A

The stem cells from the bulge forms the follicles.

24
Q

What happens when the skin is badly damaged and needs replacement?

A

When skin is badly damaged, there is a greater need for replacement cells. In this situation, bulge cells can also contribute to epidermis and sebaceous glands.

25
What happens if there is a large areas of tissue needed for restoration?
Different stem cell niches may be able to provide cells
26
What is the third stem cell niche of the epidermis?
A third stem cell niche is in the area of the dermal papilla
27
What is JEB?
Junctional epidermolysis bullosa
28
What is Junctional epidermolysis bullosa (JEB)?
This is a disorder in the epidermis where adhesion between the dermis and epidermis is impaired, patients have a muation in adhesion genes eg.LAMB3.
29
What regenerative medicine ways are being used to treat JEB?
* Skin epidermis (basal keratinocytes) can be cultured to replace skin in burn patients * Scientists are now culturing cells from JEB patients, replacing the damaged gene in cell culture, then growing it to replace the skin in the patient. * Inactivated viruses (viral vectors) can be used to introduce DNA into cells.
30
Is our gut lining continuously replinished?
Yes.
31
Why does the gut lining needs to be replinished? (2)
* The contents of the gut create a very harsh environment where cells need to be continuously replenished. * Villi increase the surface area of the intestine to aid in absorption. Cells at the ends of the villi are continuously shed
32
What are the cells of the small intestine and their functions? (6)
* Enterocyte – absorption * Goblet cells – secrete mucus * Enteroendocrine cells – secrete peptide hormones * Paneth cells – secrete anti-microbial peptides * Stem cells * submucosa cells – help to maintain the stem cell
33
Where and how does the stem cells of the small intestine proliferate?
* Stem cells at the base of the crypt proliferate, in mouse each crypt produces 12 cells per hour. Each crypt is made up of about 250 cells. * This produces a conveyor belt of cells
34
What are the two types of gene markers expressed?
Slow dividing stem cells express Bim1 Fast dividing stem cells express Lgr5 These genes are markers for stem cells
35
How do we know if Lgr5 positive cells are stem cells?
1. Lineage tracing allows us to determine the fate of a cell. 2. Transgenes can be made that cause single cells to express a marker. In this case the transgene is controlled by the promoter for Lgr5. 3. And the marker is a bacterial gene called beta galactosidase which can be used to turn cells blue. 4. The marker is expressed in the cell and in all of its offspring permanently.
36
Where can embyronic stem cells be isolated from?
Embryonic stem cells can be isolated from the epiblast and grown in cell culture.
37
How are stem cells maintained?
Specially defined conditions maintain them in the pluripotent state (BMP and LIF). This replaces the stem cell niche found in vivo.
38
What does removal of BMP/LIF cause in stem cells?
Removal of BMP/LIF causes the cells to differentiate into different cell types. Each cell type needs a specific set of conditions
39
What is the effecieny of culturing mouse embryonic stem cells?
None of these steps is very efficient – sometimes less than 1% of the cells form the desired cell type.
40
What is the difference between mouse ES (Embryonic stem cells) and human ES?
Human ES cells require different treatment than mouse ES cells (FGF + Activin) – and they appear to be pluripotent
41
What are the different assays for pluripotency?
* Expression of epiblast markers: e.g. Nanog, Oct4, Sox2, Klf4 * Chimeras are made when you mix ES cells in with a normal embryo and the ES cells contribute to different tissues in the adult. * Teratomas are benign tumours that contain differentiated tissues. * Direct the ESCs to adopt cell fates in vitro
42
How do maintenance conditions block differentiation?
The presence of LIF/BMP4 activated transcriptional factors(Epiblast markers) - Nanog Oct3/4 Sox2 Esrrb Klf4 which causes differentiation.
43
What happens if we activate epiblast marker expression in differentiated cells?
The cells dedifferentiate and become stem cells
44
What role does yamanaka factors do in formation of induced ploripotent stem cells (iPS cells)?
Yamanaka factors - Oct3/4 Sox2 Klf4 + c-Myc Differnetiate and produce induced pluripotent stem cells (iPS). | This approach means that we do not have to obtain ES cells difficultly.