In mammals, female germ cells are sheltered within somatic structures called ovarian follicles, which remain in a quiescent state until they get activated, all along reproductive life. We investigate the sequence of somatic cell events occurring just after follicle activation  . We introduce a nonlinear stochastic model accounting for the joint dynamics of  two cell types, either precursor or proliferative cells. The initial precursor cell population transitions progressively to a proliferative cell population, by both spontaneous and self-amplified processes. In the mean time, the proliferative cell population may start either a linear or exponential growing phase. A key issue is to determine whether cell proliferation is concomitant or posterior to cell transition, and to assess both the time needed for all precursor cells to complete transition and the corresponding increase in the  cell number with respect to the initial cell number. Using the probabilistic theory of first passage times, we design a numerical scheme based on a rigorous Finite State Projection and coupling techniques to assess the mean extinction time and the cell number at extinction time. We also obtain analytical formulas for an approximating branching process . We calibrate the model parameters using an exact likelihood approach using both experimental and in-silico datasets . We carry out a comprehensive comparison between the initial model and a series of submodels, which help to select the critical cell events taking place during activation . We finally interpret these results from a biological viewpoint .
In mammals, female germ cells are sheltered within somatic structures called ovarian follicles, which remain in a quiescent state until they get activated, all along reproductive life. We investigate the sequence of somatic cell events occurring just after follicle activation , starting by the awakening of precursor somatic cells, and their transformation into proliferative cells . We introduce a nonlinear stochastic model accounting for the joint dynamics of the two cell types, and allowing us to investigate the potential impact of a feedback from proliferative cells onto precursor cells. To tackle the key issue of whether cell proliferation is concomitant or posterior to cell awakening, we assess both the time needed for all precursor cells to awake, and the corresponding increase in the total cell number with respect to the initial cell number. Using the probabilistic theory of first passage times, we design a numerical scheme based on a rigorous Finite State Projection and coupling techniques to compute the mean extinction time and the cell number at extinction time. We find that the feedback term clearly lowers the number of proliferative cells at the extinction time . We calibrate the model parameters using an exact likelihood approach . We carry out a comprehensive comparison between the initial model and a series of submodels, which helps to select the critical cell events taking place during activation , and suggests that awakening is prominent over proliferation .
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either precursor or proliferative cells. The initial precursor cell population transitions progressively to a proliferative cell population, by both spontaneous and self-amplified processes. In the mean time, the proliferative cell population may start either a linear or exponential growing phase. A key issue is to determine
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also obtain analytical formulas for an approximating branching process
find that the feedback term clearly lowers the number of proliferative cells at the extinction time
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using both experimental and in-silico datasets
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