Gastrointestinal Stem Cells and EMT (16,17,18)

Question 1

What is a feature of colon epithelium?

a. There are no villi
b. There is an abundance of +4 stem cells
c. There is an absence of crypt based columnar cells
d. Paneth cells act as niche cells

Answer 1

a. There are no villi

Question 2

What are the differentiated cell types found in intestinal epithelium?

a. Enterocytes secrete mucus
b. Goblet cells secret hormones
c. Enteroendocine cells are absorptive
d. Paneth cells are immune cells

Answer 2

d. Paneth cells are immune cells

Question 3

How does Wnt signalling influence intestinal stem cells?

a. APC mutants demonstrate decreased Wnt signalling and a loss of CBC stem cells
b. Increased Wnt signalling can result in adenomatous polyps and colorectal carcinoma
c. An absence of Wnt signalling does not impact the intestinal stem cell pool
d. It down regulates Bmi1 markers to encourage +4 stem cell differentiation

Answer 3

b. Increased Wnt signalling can result in adenomatous polyps and colorectal carcinoma

Question 4

What causes familial adenomatous polyposis?

a. An inactive Wnt signalling pathway
b. A mutation in APC
c. Under expression of Beta catenin
d. Constitutive production of APC

Answer 4

b. A mutation in APC

Question 5

How can colorectal cancer be linked to stem cells?

a. Stem cells have no role in the development of colorectal cancer
b. When APC is lost in Transit Amplifying cells, rapidly proliferating adenomas develop
c. Knocking out APC in enterocytes leads to small adenomas that don’t progress
d. When APC is lost in CBC stem cells, rapidly proliferating adenomas develop

Answer 5

d. When APC is lost in CBC stem cells, rapidly proliferating adenomas develop

Question 6

Which statement is correct?

a. Lgr5+ stem cells and Paneth cells do not interact
b. Paneth cells secrete Wnt and Notch ligands and Lgr5+ stem cells express Fzd7 and Notch 1 recptors
c. Lgr5+ stem cells produce daughter cells symmetrically and by independent choice
d. Lgr5+ cells are niche components that directly influence the activity of Paneth cells

Answer 6

b. Paneth cells secrete Wnt and Notch ligands and Lgr5+ stem cells express Fzd7 and Notch 1 recptors

Question 7

What is evidence that crypt stem cell populations drift to clonality?

a. Confetti mice exhibited crypts labelled with a single fluoro chrome over a period of months
b. Confetti mice Lgr5 stem cells divided symmetrically and non-stochasitocally and always adopted the fate of a GFP labelled transit amplifying cell
c. Confetti mice exhibited villi labelled with a single fluoro chrome over a period of months
d. Confetti mice exhibited crypts and villi labelled with a single fluoro chrome over a period of months

Answer 7

a. Confetti mice exhibited crypts labelled with a single fluoro chrome over a period of months

Question 8

How do Wnt and Notch signalling regulate intestinal stem cells?

a. Notch signalling causes Lgr5 and wnt expression in stem cells
b. Cells with high levels of delta activate notch and become absorptive
c. Delta-notch signalling results in lateral inhibition between adjacent cells
d. Wnt leads to the expression of lgr5 and notch in stem cells and down-regulation of Delta in Paneth cells

Answer 8

c. Delta-notch signalling results in lateral inhibition between adjacent cells

Question 9

How does hedgehog and BMP signalling have a role in regulating the intestinal stem cell niche?

a. BMP4 is expressed in the crypt to repress Hh and Wnt signalling
b. Hh and Wnt signals from the crypt lead to BMP4 expression in the villus core
c. Disrupting hedgehog signalling can lead to ectopic crypts forming in the sides of villi
d. BMP4 expression in the villus core up regulates Hh and Wnt expression in the epithelium

Answer 9

b. Hh and Wnt signals from the crypt lead to BMP4 expression in the villus core

Question 10

How can organoids self-organise into crypts?

a. Due to BMP4 mediated crypt cell induction
b. Organoids swell when exposed to Forskolin and the addition of exogenous wnt influences crypt formation
c. Paneth cells secret wnt which induces neighbour cells to express EphB which repulse cells expressing EphrinB
d. Paneth cells secrete Delta which can degrade Lgr5+ markers and encourage crypt cell differentiation

Answer 10

c. Paneth cells secret wnt which induces neighbour cells to express EphB which repulse cells expressing EphrinB

Question 11

• Epithelial cell migration from the crypt to vilus takes 10-15 days.

Answer 11

F

Question 12

• In the stem cell zone model, it is proposed that transit amplifying cells can de-differentiate back to stem cells.

Answer 12

T

Question 13

• +4 stem cells are marked with Bmi1 and CBC stem cells are marked with Lgr5.

Answer 13

T

Question 14

• Lgr5 positive cells can only generate enterocytes and goblet cells.

Answer 14

F

Question 15

• Lgr5+ stem cells can only build crypt villus structures in vitro if a mesenchymal niche is present.

Answer 15

F

Question 16

• Culture organoids have been used to repair damage caused by colitis in the intestinal epithelium of mice.

Answer 16

T

Question 17

• The intestinal epithelium is the slowest tissue to regenerate.

Answer 17

F

Question 18

What is involved in epithelial-mesenchymal transition?

a. Mesenchymal cells are 100% individualistic
b. An extreme example of EMT is epithelial wound healing
c. Morphogenesis is a pathological form of EMT
d. The removal and repair of cells is a normal role of EMT

Answer 18

d. The removal and repair of cells is a normal role of EMT

Question 19

What occurs during EMT progression?

a. Cell junctions develop as cadherin expression increases
b. Basal lamina adhesion is lost
c. Intersital ECM is degraded
d. Basal lamina is synthesised

Answer 19

b. Basal lamina adhesion is lost

Question 20

Which family contains EMT transcription factors?

a. Snail
b. Cadherin
c. Myc
d. Sox

Answer 20

a. Snail

Question 21

Which are features of mesenchymal cells?

a. Up regulation of EcadH, Apico basal polarity, down regulation of proteases
b. Up regulation of basal lamina ECM, front back polarity, down regulation of E cadherin
c. Down regulation of E cadherin, Up regulation of interstitial ECM, front back polarity
d. Up regulation of proteases, up regulation of basement membrane, up regulation of cytokeratins

Answer 21

c. Down regulation of E cadherin, Up regulation of interstitial ECM, front back polarity

Question 22

What are the types of EMT?

a. Type 1 describes normal morphogenesis and foetal development processes
b. Type 2 describes the development of cancer cells
c. Type 3 describes processes in wound healing, inflammation and fibrosis
d. Type 4 describes processes leading to angiogenesis

Answer 22

a. Type 1 describes normal morphogenesis and foetal development processes

Question 23

What can occur during solid tissue cancer?

a. Secondary tumours are easily removed with surgery
b. Tumour initiating cells develop into circulating tumour cells
c. EMT can result in cells being resistant to apoptosis
d. Chemotherapy can remove cancer stem cells

Answer 23

c. EMT can result in cells being resistant to apoptosis

Question 24

What can solid cancer progression resemble?

a. Clonal expansion resembles stem cell progression
b. EMT to MET is resembled by cell proliferation extension
c. ECM alterations resemble stem cell development
d. Differentiation resembles EMT to MET

Answer 24

a. Clonal expansion resembles stem cell progression

Question 25

What are the CSC models? a. The dedicated model states that many cells in a cancer population are capable of becoming TIC/CSC b. The part time model states that the TIC count is always low c. The dedicated model states that there is a small amount of CSC proportion in the tumour d. The part time model states that the niche does not influence CSC regression

Answer 25

c. The dedicated model states that there is a small amount of CSC proportion in the tumour

Question 26

• Mesenchymal cells lack apical basal polarity.

Answer 26

T

Question 27

• The TIC/CSC proportion of cells in a cancer population capable of initiating a new tumour is very high.

Answer 27

F

Question 28

• Mesenchymal cell markers are present in CD44high/CD24low cells.

Answer 28

T

Question 29

• During EMT and in stem cells, E cadherin is up-regulated and wnt signalling is down-regulated.

Answer 29

F

Question 30

What does NOT happen during ENS development? a. Neural crest cells emigrate from the dorsal neural tube b. The process is independent of the foregut c. Neural crest cells migrate in a rostro-caudal direction in the gut wall d. It involves neural crest cells colonising the gastrointestinal tract

Answer 30

b. The process is independent of the foregut

Question 31

What is not a consideration for using stem cell therapy to treat Hirschsprung disease? a. The cells must be first expanded in vivo b. The cells must not induce an immune response c. There must be appropriate conditions in post natal gut d. The introduced cells must respond to cover the musculature

Answer 31

. The cells must be first expanded in vivo

Question 32

What is not a feature of the ENS that makes it favourable for stem cell therapy? a. In Hirschsprung Disease, most of the ENS is still ok b. Neural crest cells can be made from human pluripotent stem cells c. ENS organises in response to external cues only d. The ENS is still functional when not ‘perfect’

Answer 32

c. ENS organises in response to external cues only

Question 33

What is used to derive enteric neurons from hESCs? a. BMP4 b. Exogenous neurospheres c. Sox2, Oct4, C-myc and Klf4 d. Noggin

Answer 33

d. Noggin

Question 34

What was shown by graft derived neurons in the ENS? a. The project into circular muscle b. They proliferate and differentiate but cannot migrate c. They fire action potentials, but can’t receive synaptic inputs d. They are dysfunctional in vivo

Answer 34

a. The project into circular muscle

Question 35

What is Channelrhodopsin (ChR2)? a. An ion channel expressed in all mammals b. An algal ion channel that responds to electrical stimulation c. An ion channel that allows neurons to be excited by light d. An ion channel used to stimulate non-stem cell derived nerves

Answer 35

c. An ion channel that allows neurons to be excited by light

Question 36

• In the enteric nervous system, the submucosal plexus is responsible for blood flow and secretion and the myenteric plexus is responsible for peristalsis.

Answer 36

T

Question 37

• Hirschsprung disease is an acquired disorder where neurons are lost from the distal bowel.

Answer 37

F

Question 38

• In Hirschsprung disease, 95% of the gut has 100% neuron density and 5% of the gut has 0% neuron density.

Answer 38

T

Question 39

• Contractions result from inhibitory junction potentials and Relaxations result from excitary junction potential.

Answer 39

F