lecture 16: invertebrate stem cell systems and evolution of stem cells Flashcards
1
Q
Do C. elegans have stem cells?
A
- C. elegans exist as males and hermaphrodites
- no distinct females
- the only dividing cells in adults are found in the gonads
- nematode
- unsegmented round worm
- complete cell lineages have been mapped
- hermaphrodites produce both sperm and eggs
- self-fertilising
- gonad has a region of where cells undergo mitosis, and a meiotic zone
- initial meioses produce sperm which are stored in the spermatheca
- subsequently switch to producing oocytes
- as each oocyte passes through the spermatheca it is fertilised by one of the sperm that had been produced earlier
- continue to produce germ cells throughout their lifetime in the mitotic zone
- stem cell region that continues to produce these mitotic cells
- distal tip cell = stem cell niche
2
Q
What is the function of the distal tip cell?
A
- acts as a stem cell niche in the gonad and keeps germ cells in a mitotic stem cell-like state
- elongated cell that contacts all the cells in the mitotic zone
- signalling from the distal tip cell up-regulates mitosis-specific genes
- signal from the distal tip cell that activates notch signalling in the mitotic zone
- notch signal activates a protein that shuts down mitotic repressors
- when the cells move away from this signal meiosis signals get produced
3
Q
What organs in adult Drosophila contain stem cells?
A
- neuroblasts
- asymmetric divisions
- segregation of cell components
- limited number of cell divisions
- so perhaps more stem-cell like/progenitor cells
- ovary
- real stem cells that continue to produce germ cells throughout the lifetime of the organism
- testis
- real stem cells that continue to produce germ cells throughout the lifetime of the organism
- midgut
- hindgut
- renal (M.T.)
- blood (HL)
4
Q
What was the first stem cell niche to be identified?
A
- in the Drosophila ovary
- drosophila females have germline stem cells
- germarium = part of ovary → probably around 20 or so in each drosophila female, feed oocytes into the ovary
- niche cells present in red, germline stem cell in light green, daughter stem cells in dark green (cystoblasts)
- somatic stem cells allow growth and reproduction of follicle cells (encapsulate a group of germ cells)
- one of these will go on to form the oocyte, the others are nurse cells
5
Q
How are germline stem cells regulated in the ovary of the drosophila?
A
- terminal filament cells secrete a cytokine-like molecule UPD (unpaired)
- stimulates production of a BMP molecule in Cap cells
- Cap cells form the formal niche in that they are the cells that contact the GSCs but they need the signal from the terminal filament cells in order to function
- BMP molecule is received by the GMCs (BMP receptor)
- intracellular signalling cascade → shut down of production of a molecule called BAM
- as the cells move away from the niche no longer under influence of BMP so start to produce BAM → differentiation
- adherens junctions between GSCs and cap cells
6
Q
What is the adult drosophila testis?
A
- two testes in adult male
- blind ended tube
- apical part of the tube is where the stem cells are found
7
Q
What can be observed using molecular markers in the testis?
A
- the physical relationship between germline stem cells (S), somatic hub (*) and somatic stem cell progenitors (P) or stertoli-like cyst cells (C)
- slightly different system to the female
- niche = hub cells
- germ line stem cells are found in a rosette or ring around that niche
- GSCs divide in a particular orientation so that the daughter that gets pushed away from the niche is the one that differentiates
- strict orientation of the mitotic spindle
- somatic stem cells also divide
- surround the daughter of the GSC
8
Q
What is the current model of mollecular signalling in the testicular stem cell niche?
A
- UDP secreted by hub cells
- cyst stem cells also contribute to the niche for GSCs
- niche doesn’t need to be a static structure
- UDP is received by the cyst stem cells
- upregulation of BMP molecule → downregulation of BAM in GSC
- daughter pushed out of niche → upregulates BAM
- differentiation does not occur immediately
- BAM levels increase until a threshold is reached at the 16 cell stage – triggers differentiation
9
Q
What happens with a loss of BAM in the respective stem cell populations?
A
- loss of Bam (mutant) in an ovary causes a proliferation of germline stem cells
- loss of Bam (mutant) in a testis causes a proliferation of spermatogonia (16-32-64 etc)
10
Q
How is the adult drosophila midgut epithelium maintained?
A
- maintained by a population of multipotent stem cells
- ISC
- basally located
- largest cells are the enterocytes - absorptive cells of the intestinal epithelium
- also find enteroendocrine cells and enteroblast (transient cell type)
- only cells undergoing division are the stem cells (cf human gut), not TAs
- enteroblast will differentiate to either and enterocyte or enteroendocrine cell depending on what signals it receives
11
Q
What happens with a loss of APC in the midgut epithelium?
A
- hyperplasia
- stem cells pretty much form a mono layer around the edge of the intestine
- with loss of APC you see multilayering, hyperplasia
- looks like an intestinal polyp
12
Q
What is colorectal or bowel cancer?
A
- colorectal cancer has the highest incidence of all malignant cancers in australia
- 1/17 lifetime risk for men
- 1/26 lifetime risk for women
- colorectal cancer is the second most common cause of cancer death (after lung cancer)
- increased Wnt signalling in the intestinal epithelium results in adenomatous polyps that develop into colorectal carcinoma
- drosophila could be a good model for this
13
Q
Where did stem cells arise in metazoan evolution?
A
- ancestral colonial choanoflagellate
- sponges are the most ancestral of the animals (but suggested comb jellies (Ctenophores) may sit basal to porifera)
- if Ctenophores are more basal suggests that muscles must have evolved twice in the evolution of the animal kingdom
- sponges are however very simple animals with stem cells
14
Q
What is the tissue structure of sponges?
A
- layers of cells but no “real” tissues or organs
- different cell types in layers
- no neurons or muscle
- no epithelial tissue
- loose arrangement of cells
- “mesenchyme”-like
- water pumped in through porocytes into the central cavity
- pumped out hole in top called osculum
- surrounding central cavity are cells called choanoctes
- has a flagellum
- phagocytosis of food particules
- passed on to amoebocyte
- look for all the world like another type of organism: choanoflagellate → suggested sponges are derived from these
15
Q
What is a choanoflagellate colony?
A
- perhaps the origin of sponges
16
Q
What are properties of archeocytes (amoebocytes) and choanocytes?
A
- both have stem cell properties
- archeocytes and choanocytes both express a member of the Piwi family of proteins – these proteins are restricted to the germline in most higher metazoans but found in stem cell populations in planaria and cnidaria
- Human Piwi has also been found in haemtopoietic stem cells
- archeocytes can renew themselves and differentiate into various other cell types
- choanocytes can dedifferentiate into archeocytes and also directly produce gametes (archeocytes can also produces gametes)
- Piwi play a role in stabilising the genome
17
Q
What is a model of stem cell evolution?
A
- the ancestral metazoan was a conglomerate of unicellular flagellates (choanocyte-like)
- proliferation became restricted to a subset of cells, allowing other cells to specialise in function
18
Q
What are the stem cell populations in plants?
A
- plant meristems
- since stem cells are found in plants it means they either evolved twice or evolved before the animal/plant split
- shoot apical meristem
- root apical meristem
19
Q
What is seen in the growing root meristem?
A
- the growing root meristem shows zones of cell division, elongation and differentiation
- plants are restricted in that they have cell walls which means they don’t have the same flexibility that animal cells do
- elongation is laying down of microtubules within the cells in a particular direction
- cells grow essentially by expanding along one axis
20
Q
What maintains the meristem?
A
- cell signalling maintains the meristem, although plants use many different signals to animals
- a short-range signal produced by the Wuschel-expressing cells maintains the meristem and a signal secreted by the meristem (Clavata3) feeds back to limit the size of the Wuschel domain and hence the size of the meristem
- similar feedback systems are used in animals
21
Q
What was metazoan evolution?
A
- comb jellies in a more basal layer has caused some confusion
22
Q
review points:
A
- what is the distal tip cell in C. elegans?
- how do the drosophila male and female germline stem cell niches resemble each other and how are they different?
- what is similar about drosophila and vertebrate intestinal stem cell niches (wnt signalling)?
- what are the sponge stem cells (archeocytes, choanocytes)?
- what is a model of stem cell evolution?
- where are plant stem cells located?
- how does a feedback system maintain the meristem?
