Several distinct differentiation protocols for deriving pancreatic progenitors (PPs) from human pluripotent stem cells have been described, but it remains to be shown how similar the PPs are across protocols and how well they resemble their in vivo counterparts. Here, we evaluated three differentiation protocols, performed RNA and assay for transposase-accessible chromatin using sequencing on isolated PPs derived with these, and compared them with fetal human pancreas populations. This enabled us to define a shared transcriptional and epigenomic signature of the PPs, including several genes not previously implicated in pancreas development. Furthermore, we identified a significant and previously unappreciated cross-protocol variation of the PPs through multi-omics analysis and demonstrate how such information can be applied to refine differentiation protocols for derivation of insulin-producing beta-like cells. Together, our study highlights the importance of a detailed characterization of defined cell populations derived from distinct differentiation protocols and provides a valuable resource for exploring human pancreatic development.

已经描述了几种从人类多能干细胞中衍生胰腺祖细胞 (PPs) 的不同分化方案，但仍有待证明 PPs 在不同方案之间的相似程度以及它们与体内的相似程度同行。在这里，我们评估了三种分化方案，对由此衍生的分离 PP 进行测序，对转座酶可及染色质进行 RNA 和测定，并将它们与胎儿人类胰腺群体进行比较。这使我们能够定义 PP 的共享转录和表观基因组特征，包括以前未涉及胰腺发育的几个基因。此外，我们通过多组学分析确定了 PP 的一个重要的和以前未被重视的交叉协议变异，并展示了如何应用这些信息来改进分化协议以衍生产生胰岛素的 β 样细胞。一起，