Figure 1.

A summary of the pivotal stages of pancreatic differentiation. (A) Mammalian pancreas development based on knowledge from both rodent and human studies. The signaling pathways suggested to be positively regulating the differentiation process are highlighted in green, while those found to be inhibited in order to drive differentiation toward pancreatic lineage are shown in red. (B) An in vitro pancreatic differentiation timecourse generating β-like cells from hPSCs. The signaling pathways (green) and antioxidants (pink) that are positively regulating the differentiation process at each phase of development are highlighted. Stage-specific signaling pathways that are inhibited to drive differentiation toward pancreatic lineage are shown in red. The decreasing doses of RA used during the differentiation process [as described by Rezania et al. (6) and Pagliuca et al. (7)] are represented by the decreasing shades of green. The differing colors co-existing in an aggregate illustrates the heterogeneity of cells prevalent in such a differentiation scheme. While some of the cells will transit from being endocrine progenitors (light orange) to Pdx1⁺ insulin-producing β-like cells (brown), the end-product will include an assortment of maturing endocrine cell types (represented by orange and light orange).