lecture 16: invertebrate stem cell systems and evolution of stem cells Flashcards Preview

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Flashcards in lecture 16: invertebrate stem cell systems and evolution of stem cells Deck (22):
1

 Do C. elegans have stem cells?

  • 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

What is the function of the distal tip cell?

  • 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

What organs in adult Drosophila contain stem cells?

  • 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

What was the first stem cell niche to be identified?

  • 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

How are germline stem cells regulated in the ovary of the drosophila?

  • 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

What is the adult drosophila testis?

  • two testes in adult male
  • blind ended tube
  • apical part of the tube is where the stem cells are found 

7

What can be observed using molecular markers in the testis?

  • 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

What is the current model of mollecular signalling in the testicular stem cell niche?

  •  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

What happens with a loss of BAM in the respective stem cell populations?

  • 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

How is the adult drosophila midgut epithelium maintained?

  • 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

What happens with a loss of APC in the midgut epithelium?

  • 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

What is colorectal or bowel cancer?

  • 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

Where did stem cells arise in metazoan evolution?

  • 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

What is the tissue structure of sponges?

  • 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

What is a choanoflagellate colony?

  • perhaps the origin of sponges

16

What are properties of archeocytes (amoebocytes) and choanocytes?

  • 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

 What is a model of stem cell evolution?

  • 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

What are the stem cell populations in plants?

  • 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

What is seen in the growing root meristem?

  • 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

What maintains the meristem?

  • 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

What was metazoan evolution?

  • comb jellies in a more basal layer has caused some confusion

22

review points:

  • 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?