Figure 8. Acinar suppression and pan-endocrine activation precedes subtype-specific gene activation in acinar to β-cell conversion.
In acinar to β-cell conversion induced by M3 (Ngn3+Mafa+Pdx1), near complete suppression of the acinar factor Mist1 was observed in the Cherry+-infected cells at day 2 (A). The pan-endocrine factor Pax6 was also robustly induced at day 2 (B). The Mist1−Pax6+ state was maintained in the majority of Cherry+ cells at later time points (E, F, I, J). In contrast, β-subtype specific factors insulin and Nkx6.1 were not induced until day 5 (G, H) and became more robustly expressed at day 10 (K, L). In control samples expressing cherry alone, the majority of cherry+ acinar cells had Mist1 expression (M), and none had induced endocrine gene expression (N, O, P). Quantifications are shown as mean ± s.d (Q). At least 1000 cherry+ cells counted from three different animals.