23 MAR 2011
HMB321 L18: Bret Pearson, Planarians a new model to disease and regeneration
-How to establish new human disease models?
-Prebilateria (not bilaterally symmetric,e.g.Sponge and jellyﬁsh)
-Branches into ecdysozoa and deuterostomes (invertebrates;vertebrates)
-As well as lophotrochozoa (diverse species,e.g.Annelids,snails,molluscs)
How to bring new system into the lab?
-Organism should have“special advantages”
-Study adult stem cells
-Develop tools and culture conditions
Planarians and Adult Stem Cells
-Adult stem cell
-Large uncondensed nucleus is a key characteristic (how it was found)
-Non-stem cells are differentiated and have condensed,small nuclei
-Important for tissue homeostasis,injury regeneration => longevity?
-E.g. C. Elegans have 0 divisions and live only 4 days, whereas mice have more divisions
and live up to 3 years,whereas humans have more divisions than mice and live 80 years
-Planarians seem to be immortal,i.e.Their division rate seems inﬁnite = immortal?
-Stem cell is only as good as the lineage that it outputs
-Maintenance of correct lineage is unknown process,especially in vertebrates
-This maintenance goes awry in our 20s-30s => organismal senescence vs. Cancer (in
developed countries,in about 1 in 3 humans;hyper-proliferative)
-How stem cells accomplish their lineages?
-Hierarchal => start with Non-stem cell (somatic cell) provides info for adult stem cell (ASC)
-Cell-cell signalling occurs between Niche &ASC
-Stem cells are deﬁned by unique biology of self-renewal (multipotency)
-Progenitor Cells => changes in gene expression for particular line starting
-Post-mitotic progeny => differentiated cells (humans replace 10^10 cells per day;
maintenance of homeostasis)
-Last process = proliferation control?
-Tumour suppressors => can you ﬁgure this out from stem cells to work around
cancer?To ﬁgure out how things go awry?
Challenges in studying adult stem cells
-Unknown cellular lineages
-Cells don’t divide well in culture
-Manipulation of adults is difﬁcult/time consuming (i.e.Decade-long streams in adult cells)
-Accessibility in adults is almost impossible (i.e.Can’t watch the stem cells do anything)
What are planarians?
-Planarians are the garbage can of evolution? -TH Morgan,1911
-Got them into the laboratory;his early work was not fruitﬂy based,but Planarians
-He tried to slice the Planarian in different ways to ﬁgure out if it would regenerate wrong
-Found that each piece he could off => made an entirely proportionate worm (like
reproduction);incredible regeneration,just takes time
-Always thought that if you cut off the head => must have polarity => will grow back as a head
or nothing at all
-The Planarian just grew into a new worm
-Using ISH => found that 10-20% of the worm are made of stem cells
-A smaller proportion are the actively dividing cells
-So,how do intact planarians regulate theirASC?
-So,how do the stem cells change regulation during regeneration?
-There are different domains of proliferation after injury
-Hyperproliferation of cells at the anterior end to make brain tissue => need to decrease/down
-If you artiﬁcially KO B-catenin => will produce 2 heads
-In tail tissue => B-cat up,p53
-KO B-cat,produces 2 ﬁns
Planarians in the lab
-Cheap and easy maintain (small-scale management,eats liver,etc)
-Increase pop’n through amputations => clones!
Injury causes temporary stem cell hyper-proliferation
-All regions can be cut to regenerate
-How can injury cause hyper-proliferation?What are the processes (similar toASC?)?
Stem cell numbers change with nutrient levels