Lecture 15 - Stem Cell Basics Flashcards

1
Q

What is the epiblast?

A

Stage of embryonic development that gives rise to the germ layers (ectoderm, mesoderm, endoderm).

Begins around the time of implantation into the uterus

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2
Q

How do cell differentiation and determination occur?

A

Epigenetic changes (alterations to chromatin)

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3
Q

Determination

A

Occurs before overt differentiation.

Not morphologically obvious

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4
Q

Differentiation

A

Result of changes in gene expression
Commitment to a cell lineage
Cell changes morphologically so that it can carry out particular function

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5
Q

Transdifferentiation

A

A cell committed to one lineage switches pathways to another lineage.

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6
Q

Examples of transdifferentiation

A

Intestinal metaplasia of the oesophagus.

Squamous metaplasia of the intestinal tract.

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7
Q

Can transdifferentiation be induced?

A

Yes. In cell culture, ectopic expression of master regulator transcription factors

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8
Q

Example of transdifferentiation between two closely-related cell types

A

Pancreatic-lineage cells can transdifferentiate into hepatocytes

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9
Q

Intestinal metaplasia

A

Damage to the oesophageal epithelium through acid reflux leads to conversion of normal squamous epithelium into intestinal epithelium.

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10
Q

Danger of intestinal metaplasia of the oesophagus

A

Is a precursor to oesophageal adenocarcinoma

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11
Q

Stem cell that can give rise to several types of mature cell

A

Multipotent

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12
Q

Stem cell that can give rise to any mature cell

A

Pluripotent

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13
Q

Stem cell that can give rise to a new individual, given appropriate support

A

Totipotent

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14
Q

Types of adult tissue
1)
2)
3)

A

1) Continuously renewing
2) Conditionally renewing
3) Non renewing

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15
Q

Example of continuously renewing adult tissues

A

Bone marrow, skin, gut

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16
Q

Examples of conditionally renewing adult tissues

A

Liver, kidneys (to a lesser extent)

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17
Q

Example of a non renewing adult tissue

A

Cardiac muscle

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18
Q

How often is the lining of the GIT replaced?

A

Once every four days

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19
Q

Number of cells lost each day form each person

A

~20 billion

20
Q

What is a stem cell?

A

Primitive, undifferentiated cell that can give rise to more specialised cell types or renew itself.

21
Q
Features of stem cells 
1)
2)
3)
4)
5)
6)
A

1) Capable of self-renewal and differentiation
2) May give rise to transit amplifying cells (compartment-committed cells with a limited division capacity)
3) Often lack specialised organelles, have a high nucleus:cytoplasm ratio
4) Express telomerase (long-lived)
5) Slowly-dividing
6) Few in number

22
Q

How do stem cells normally sit in the body?

A

Restricted to specific niches

23
Q

Adult-tissue stem cell features
1)
2)

A

1) Tightly regulated function by powerful transcription factors
2) In an altered environment, tight transcriptional regulation might be relaxed, leading to plasticity.

24
Q
Ways to identify stages of differentiation 
1)
2)
3)
4)
A

1) Transcription factors
2) Surface molecules (EG: CD)
3) Cytostructural molecules (EG: intermediate filaments)
4) Specific functional gene products

25
Q

Regions of the brain that are stem-cell niches
1)
2)

A

1) Subventricular

2) Hippocampal

26
Q

Where do neurons from the subventricular zone end up?

A

In the olfactory epithelium

27
Q

What might hippocampal neurogenesis have a role in?

A

Memory

28
Q

Number of cell types in the gut that constantly form from stem cells

A

Four (goblet, paneth, enteroendocrine, enterocyte)

29
Q

Where in the gut do stem cells sit?

A

Crypts

30
Q

Paneth cell role

A

Gut innate immunity.

Produce defensins and lysosome

31
Q

Signalling pathways that regulate crypt stem cell differentiation

A

Wnt

Notch

32
Q

Where in the hair follicle do stem cells sit?

A

The bulge

33
Q

Signalling pathways involved in hair follicle stem cell regulation

A

BMP

Wnt

34
Q

How do stem cells in body niches often behave?

A

Quiescent stem cells that are not dividing are a tissue reserve that is activated upon damage.

Quiescent stem cells give rise to active or progenitor stem cells which are responsible for homeostasis under normal circumstances

35
Q

Type of stem cells in the liver

A

Facultative stem cells (can conditionally renew)

36
Q

Where are liver stem cells found?

A

Bipotential stem cells found in the biliary tree

37
Q

How can the liver regenerate?

A

Either by hepatocyte proliferation or from bipotential stem cells in the biliary tree

38
Q

How can the liver’s regenerative ability be impaired?

A

Cirrhosis, viral infection can lead to scarring,

39
Q

Factors added to fibroblasts to make them become pluripotent stem cells

A

Yamanaka factors

40
Q

Three sources of stem cells

A

1) Embryonic
2) iPS
3) Somatic cell nuclear transfer

41
Q

Properties of pluripotent stem cells
1)
2)
3)

A

1) Grow indefinitely in vitro
2) Capable of colonising all tissues after injection into a blastocyst (chimaeric animal)
3) Maintain normal genetic makeup

42
Q

At which stage do stem cells switch from being totipotent to pluripotent?

A

At around the 4-8 cell stage

43
Q
Signalling systems that control animal development
1)
2)
3)
4)
5)
6)
7)
A

1) Wnt
2) Hedgehog
3) Notch
4) TGFb
5) Tyr kin
6) Nuclear rec
7) Jak/Stat

44
Q
Yamanaka factors to induce pluripotency
1)
2)
3)
4)
A

1) Oct-4
2) Sox2
3) Klf4
4) C-myc

45
Q

How are Yamanaka factors introduced to cells?

A

Viral transfection

46
Q
Possible application of iPS in biomedical research
1)
2)
3)
4)
A

1) Basic studies of human development and disorders
2) Functional genomics of human cells
3) Discovery of novel factors controlling tissue regeneration and repair
4) In vitro models for drug discovery, toxicology

47
Q

Particular use for iPS in studying human development

A

Human brain development is very different to that of other animals
iPS can be used to model human cortical development, model developmental diseases such as autism, schizophrenia, epilepsy