近日，美国威尔康奈尔医学院教授Shuibing Chen及其团队的研究认为ChemPerturb-seq筛选确定了一种小分子鸡尾酒，可提高人皮下移植后β细胞的存活率。2025年6月24日，国际知名学术期刊《细胞—干细胞》发表了这一成果。

该团队将化学筛选与单细胞RNA测序（scRNA-seq）相结合，进行化学扰动-seq (ChemPerturb-seq)，能够系统分析单个小分子处理后人类β细胞的分子变化。利用这个平台，研究团队进行了体内条形码筛选，发现了一种小分子鸡尾酒，包括β-脂蛋白61-91、胰岛素生长因子-1和前列腺素E2，在将人类β细胞和原代胰岛移植到雌性小鼠皮下时，它们显著提高了功能和存活率，而不是移植到雄性小鼠身上。研究团队发现了另外两种分子，血清素和组胺，当它们皮下移植到雄性小鼠身上时，可以促进胰岛功能。这种小分子鸡尾酒可以用于改进目前FDA批准的胰岛移植程序。最后，该课题组开发了一个人工智能（AI）驱动的网站ChemPerturbDB，它提供了广泛的ChemPerturb-seq数据集的热友好开放访问分析。

据悉，传统的化学筛检侧重于每个筛检的单一检测，这使得它们劳动密集且成本高昂。

附：英文原文

Title: ChemPerturb-seq screen identifies a small molecule cocktail enhancing human beta cell survival after subcutaneous transplantation

Author: J. Jeya Vandana, Jiajun Zhu, Alice Maria Giani, Tuo Zhang, Lauretta A. Lacko, Dongliang Leng, D. Leland Taylor, Brian N. Lee, Zhaowei Han, Tiancheng Jiao, Yuanhao Huang, Meiqi Zhao, Xinyi Liu, Angie Chi Nok Chong, Dongxiang Xue, Zihe Meng, Jenny Z. Xiang, Chendong Pan, Wei Wang, Ali Naji, Todd Evans, Jie Liu, Francis S. Collins, Chengyang Liu, Shuibing Chen

Issue&Volume: 2025-06-24

Abstract: Traditional chemical screens have focused on a single assay per screen, making them labor intensive and costly. Here, we combined a chemical screen with single-cell RNA sequencing (scRNA-seq) to perform Chemical Perturb-seq (ChemPerturb-seq), enabling a systematic analysis of the molecular changes of human beta cells upon individual small molecule treatments. Using this platform, we performed an in vivo barcoded screen and discovered a small molecule cocktail, including beta-lipotropin 61-91, insulin growth factor-1, and prostaglandin E2, with which preconditioning human beta cells and primary islets significantly enhanced function and survival when transplanted subcutaneously to female, but not to male, mice. We identified two additional molecules, serotonin and histamine, that promote islet function when transplanted subcutaneously to male mice using ChemPerturb-seq. Such small molecule cocktails could be applied to improve the current FDA-approved islet transplantation procedure. Finally, we developed an artificial intelligence (AI)-powered website, ChemPerturbDB, which provides user-friendly open access analysis of the extensive ChemPerturb-seq dataset.

DOI: 10.1016/j.stem.2025.06.002

Source: https://www.cell.com/cell-stem-cell/abstract/S1934-5909(25)00224-3