Naive and primed human pluripotent stem cells (hPSC) provide valuable models to study cellular and molecular developmental processes. The lack of detailed information about cell-surface protein expression in these two pluripotent cell types prevents an understanding of how the cells communicate and interact with their microenvironments. Here, we used plasma membrane profiling to directly measure cell-surface protein expression in naive and primed hPSC. This unbiased approach quantified over 1,700 plasma membrane proteins, including those involved in cell adhesion, signaling, and cell interactions. Notably, multiple cytokine receptors upstream of JAK-STAT signaling were more abundant in naive hPSC. In addition, functional experiments showed that FOLR1 and SUSD2 proteins are highly expressed at the cell surface in naive hPSC but are not required to establish human naive pluripotency. This study provides a comprehensive stem cell proteomic resource that uncovers differences in signaling pathway activity and has identified new markers to define human pluripotent states.

天真和初免的人类多能干细胞（hPSC）提供了有价值的模型来研究细胞和分子的发育过程。在这两种多能细胞类型中，缺乏有关细胞表面蛋白表达的详细信息，使人们无法了解细胞如何与微环境交流和相互作用。在这里，我们使用质膜分析法直接测量幼稚和引发的hPSC中细胞表面蛋白的表达。这种无偏方法量化了1,700多种质膜蛋白，包括那些参与细胞粘附，信号传导和细胞相互作用的蛋白。值得注意的是，在幼稚的hPSC中，JAK-STAT信号上游的多个细胞因子受体更为丰富。此外，功能实验表明，FOLR1和SUSD2蛋白在幼稚的hPSC中在细胞表面高度表达，但不需要建立人类幼稚的多能性。这项研究提供了全面的干细胞蛋白质组学资源，该资源揭示了信号通路活性的差异，并确定了定义人类多能状态的新标记。