Lecture 15 - Stem Cell Basics Flashcards Preview

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Flashcards in Lecture 15 - Stem Cell Basics Deck (47):
1

What is the epiblast?

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

Begins around the time of implantation into the uterus

2

How do cell differentiation and determination occur?

Epigenetic changes (alterations to chromatin)

3

Determination

Occurs before overt differentiation.
Not morphologically obvious

4

Differentiation

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

5

Transdifferentiation

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

6

Examples of transdifferentiation

Intestinal metaplasia of the oesophagus.
Squamous metaplasia of the intestinal tract.

7

Can transdifferentiation be induced?

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

8

Example of transdifferentiation between two closely-related cell types

Pancreatic-lineage cells can transdifferentiate into hepatocytes

9

Intestinal metaplasia

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

10

Danger of intestinal metaplasia of the oesophagus

Is a precursor to oesophageal adenocarcinoma

11

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

Multipotent

12

Stem cell that can give rise to any mature cell

Pluripotent

13

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

Totipotent

14

Types of adult tissue
1)
2)
3)

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

15

Example of continuously renewing adult tissues

Bone marrow, skin, gut

16

Examples of conditionally renewing adult tissues

Liver, kidneys (to a lesser extent)

17

Example of a non renewing adult tissue

Cardiac muscle

18

How often is the lining of the GIT replaced?

Once every four days

19

Number of cells lost each day form each person

~20 billion

20

What is a stem cell?

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

21

Features of stem cells
1)
2)
3)
4)
5)
6)

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

How do stem cells normally sit in the body?

Restricted to specific niches

23

Adult-tissue stem cell features
1)
2)

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

24

Ways to identify stages of differentiation
1)
2)
3)
4)

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

25

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

1) Subventricular
2) Hippocampal

26

Where do neurons from the subventricular zone end up?

In the olfactory epithelium

27

What might hippocampal neurogenesis have a role in?

Memory

28

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

Four (goblet, paneth, enteroendocrine, enterocyte)

29

Where in the gut do stem cells sit?

Crypts

30

Paneth cell role

Gut innate immunity.
Produce defensins and lysosome

31

Signalling pathways that regulate crypt stem cell differentiation

Wnt
Notch

32

Where in the hair follicle do stem cells sit?

The bulge

33

Signalling pathways involved in hair follicle stem cell regulation

BMP
Wnt

34

How do stem cells in body niches often behave?

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

Type of stem cells in the liver

Facultative stem cells (can conditionally renew)

36

Where are liver stem cells found?

Bipotential stem cells found in the biliary tree

37

How can the liver regenerate?

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

38

How can the liver's regenerative ability be impaired?

Cirrhosis, viral infection can lead to scarring,

39

Factors added to fibroblasts to make them become pluripotent stem cells

Yamanaka factors

40

Three sources of stem cells

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

41

Properties of pluripotent stem cells
1)
2)
3)

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

42

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

At around the 4-8 cell stage

43

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

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

44

Yamanaka factors to induce pluripotency
1)
2)
3)
4)

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

45

How are Yamanaka factors introduced to cells?

Viral transfection

46

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

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

Particular use for iPS in studying human development

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