Mary Teruel, Stanford, Conrolling size of tissue with stochastic noises

Mary Teruel, Stanford, Conrolling size of tissue with stochastic noises

Spalinding 2008 nature, fat cells renew at 10% per year.

PPARG -> adipogenic factors --> change of preadipocytes to adipcytes.

Park et al, Cell Rep 2012, conversion of preadipocyte to adipocyte via a bistable switch. (All or none process)
[PPARgamma] ~ [C/EBPbeta] plot to show bi-modal distribution of two cell populations.

[PPARG] ~ Rosiglitzaone(uM) plot show hysteresis, in support of bistable switch and positive feedback.

Increased noises would lead to more switches, this can be easily shown by simulation.

Q: how to increase noises experimentally?

More noises lead to stronger de-differentiation.

Too little noise, hard to switch. Too much noise, cannot hold the states.

One-feedback loop model:
 R ->    PPARG(x0)    --> Terminal
         |->CEBPA(x1)-^
Two ODE equations.

Increased cooperativity helps, but does not solve the optimzation problem.

Multi-loop systems can solve the optimization problem in theory. How to prove this in experiments?

MT uses a triple-quadropole mass spectrometer, aiming to identify feedback loops.  This method requires a unique peptide sequence. Time course data were obtained. 7 feedback loop were concluded.

Fat cells -> nuclei -> proteins ---(typsin)---> peptides ---> mass spec

References:
http://q-bio.org/w/images/c/c3/Talk_TeruelMary.pdf