Identification of ALPPL2 as a Naive Pluripotent State-Specific Surface Protein Essential for Human Naive Pluripotency Regulation
Identification of ALPPL2 as a Naive Pluripotent State-Specific Surface Protein Essential for Human Naive Pluripotency Regulation
复制标题
鉴定 ALPPL2 作为人类初始多能性调节所必需的初始多能状态特异性表面蛋白。
DOI：
10.1016/j.celrep.2020.02.090
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发表时间：
2020-03-17
期刊：
影响因子：
8.8
通讯作者：
Gao, Shaorong
中科院分区：
文献类型：
--
作者：
Bi, Yan;Tu, Zhifen;Gao, Shaorong
从植入前囊胚的外胚层建立的人类幼稚多能干细胞为多能性调节和谱系分化的机制研究提供了有用的模型。在优化培养条件和定义初始多能性的分子标准方面已经取得了重要进展。然而，幼稚特异性表面标记的身份和幼稚多能性调节的潜在分子机制仍然知之甚少。在这里，我们通过系统的蛋白质组学和转录组学分析，将碱性磷酸酶胎盘样 2 (ALPPL2) 确定为一种突出的幼稚特异性表面标记。此外，我们证明 ALPPL2 对于初始多能性的建立和维持至关重要。此外，我们发现 ALPPL2 可以与 RNA 结合蛋白 IGF2BP1 相互作用，稳定幼稚多能性转录因子 TFCP2L1 和 STAT3 的 mRNA 水平，从而调节幼稚多能性。总体而言，我们的研究确定了人类幼稚多能性的功能表面标记，为人类幼稚多能性相关机制研究提供了强大的工具。
Human naive pluripotent stem cells established from the epiblasts of preimplantation blastocysts provide a useful model for mechanistic studies of pluripotency regulation and lineage differentiation. Important advances have been made to optimize culture conditions and define molecular criteria for naive pluripotency. However, the identity of naive-specific surface markers and the underlying molecular mechanism of naive pluripotency regulation remain poorly understood. Here, we identify alkaline phosphatase placental-like 2 (ALPPL2) as a prominent naive-specific surface marker by systematic proteomic and transcriptomic analyses. Furthermore, we demonstrate that ALPPL2 is essential for both the establishment and maintenance of naive pluripotency. Moreover, we show that ALPPL2 can interact with the RNA-binding protein IGF2BP1 to stabilize the mRNA levels of the naive pluripotency transcription factors TFCP2L1 and STAT3 to regulate naive pluripotency. Overall, our study identifies a functional surface marker for human naive pluripotency, providing a powerful tool for human-naive-pluripotency-related mechanistic studies.