Lecture 2 - Mouse Embryonic Stem Cells Flashcards
Teratomas
Benign tumours containing derivatives of 3 germ layers
Teratocarcinomas
Malignant tumours, contain undifferentiated cells
Embryonal Carcinoma Cells
Cells isolated from the undifferentiated cells of teratocarcinomas
LIF
Leukemia Inhibitory Factor, a cytokine
Oct3/4 is required for pluripotency
TRUE OR FALSE
TRUE
Too much or too little Oct3/4 is bad, Goldilocks!
LIF inhibits differentiation how?
LIF inhibits differentiation via activation of STAT3 (a transcription factor), leading to a cell fate of self-renewal instead of differentiation
However LIF also promotes differentiation via he ERK/MAPK pathway in mESCs
Oct3/4 is a target of STAT3
TRUE OR FALSE
FALSE
Oct3/4 is not a target of STAT3
LIF can prevent differentiation by itself
TRUE OR FALSE
FALSE
LIF alone cannot prevent differentiation
Inhibition of FGFR/Erk prevents differentiation, since FGF and FGFR are the main drivers of differentiation
The “Ground State” hypothesis
Embryonic Stem Cells represent the “ground state” of pluripotency
This means that there is no special signal that is required to instruct the cells to remain undifferentiated, they only need to protect them from differentiating inducing signals (e.g. FGF)
Nanog supports LIF-independent self-renewal
TRUE OR FALSE
TRUE
Mouse Embryonic Stem Cells
- Derived from pre-implantation embryos
- Express Oct3/4, Nanog, Rex1, Stella
- Self-renew under influence of LIF
- Differentiate under influence of FGF/Erk
Epiblast Stem Cells
- Behave like human ESCs
- Pluripotent
- Taken from the epiblast (one layer in the inner cell mass of the blastocyst)
Naive and Primed States
mESCs:
-2i stabilises a “naive” phentoype
-EpiSC represent a pure stable “primed” state
-Other states may be possible (e.g. “2C”)
hESC
-Initially only “primed”
-More recent reports of “naive state” in hESCs