Multiple origins and modularity in the spatiotemporal emergence of cerebellar astrocyte heterogeneity
Fig 9
Rules and outcome of the simulation model applied to E12 lineages.
(A,B) The schematic representation in (A) shows the distinct fate transitions allowed in the model (indicated by the arrows). The probability of MP proliferation is kept constant at 0.465 in the simulations of E12-P30 lineages. Each daughter cell of each division either remains an MP or differentiates into a postmitotic astrocyte. In this latter case, the probabilities of generating the distinct astrocyte subtypes (BG versus GLA versus WMA) are generation-dependently set according to the birthdating experiments performed in the hemispheres, as shown in (B). Histograms in (C-E) show the outcomes of the simulated lineages compared to the experimental data. Simulated clone sizes (C) appear quite similar to those of the observed clones. On the other hand, the proportions of astrocyte subtypes are not well represented, with too many WMAs and BG produced (D). Same color code as in (A). Similarly, the model fails to recapitulate the proportions of clone subtypes (E; E12-P30). (F,G) Simulated and observed lineages were compared at P0 (corresponding to generation 6). Too many HetCs (F) are found in simulated lineages compared to empirical clones, because of the generation of too many PWM+cortical clones at the expense of both cortical and PWM families (G). ***, P < 0.001; P values are calculated with chi-squared test. Cortical clones comprise PCLp HomCs, GLAp HomCs, and PCLp+GLAp HetCs; Cortical+PWM clones comprise PCLp+PWM, GLAp+PWM, and PCLp+GLAp+PWM HetCs. The numerical data used in panels (B-G) are included in S1 Data. BG, Bergmann glia; E, embryonic day; GLA, granular layer astrocyte; GLAp, granular layer astrocyte precursor; HetC, heterogeneous clone; HomC, homogeneous clone; MP, multiple progenitor; P, postnatal day; PCLp, Purkinje cell layer precursor; PWM, prospective white matter; WMA, white matter astrocyte.