美国哈佛医学院George M. Church和德国德累斯顿再生疗法中心（CRTD）Volker Busskamp课题组合作取得最新进展。他们建立了用于细胞命运工程的人类转录因子（TF）综合库。相关论文于2020年11月30日发表于《自然-生物技术》杂志上。

为了能够系统地探索由TF介导的编程环境，他们提出了人TFome，这是一个全面的库，其中包含1,564个TF基因和1,732 TF剪接亚型。通过筛选三个人类多能干细胞（hPSC）品系文库，他们发现了290个TF，其中包括241个以前未报道的TF，它们在4天内诱导分化，而没有改变外部可溶性或生物力学因素。

他们使用了四个命中点将hPSC编程为与原代细胞具有分子和功能相似性的神经元、成纤维细胞、少突胶质细胞和血管内皮样细胞。他们利用细胞自动化程序使hPSC可以同时并行编程为多种单元类型。他们还通过将少突胶质细胞诱导的hPSC与未修饰的hPSC生成大脑类器官，从而促进原位髓鞘形成，从而证明了正交编程。人TFome的大规模组合筛选将补充基于发育生物学和计算系统生物学的细胞工程其他策略。

附：英文原文

Title: A comprehensive library of human transcription factors for cell fate engineering

Author: Alex H. M. Ng, Parastoo Khoshakhlagh, Jesus Eduardo Rojo Arias, Giovanni Pasquini, Kai Wang, Anka Swiersy, Seth L. Shipman, Evan Appleton, Kiavash Kiaee, Richie E. Kohman, Andyna Vernet, Matthew Dysart, Kathleen Leeper, Wren Saylor, Jeremy Y. Huang, Amanda Graveline, Jussi Taipale, David E. Hill, Marc Vidal, Juan M. Melero-Martin, Volker Busskamp, George M. Church

Issue&Volume: 2020-11-30

Abstract: Human pluripotent stem cells (hPSCs) offer an unprecedented opportunity to model diverse cell types and tissues. To enable systematic exploration of the programming landscape mediated by transcription factors (TFs), we present the Human TFome, a comprehensive library containing 1,564 TF genes and 1,732 TF splice isoforms. By screening the library in three hPSC lines, we discovered 290 TFs, including 241 that were previously unreported, that induce differentiation in 4 days without alteration of external soluble or biomechanical cues. We used four of the hits to program hPSCs into neurons, fibroblasts, oligodendrocytes and vascular endothelial-like cells that have molecular and functional similarity to primary cells. Our cell-autonomous approach enabled parallel programming of hPSCs into multiple cell types simultaneously. We also demonstrated orthogonal programming by including oligodendrocyte-inducible hPSCs with unmodified hPSCs to generate cerebral organoids, which expedited in situ myelination. Large-scale combinatorial screening of the Human TFome will complement other strategies for cell engineering based on developmental biology and computational systems biology. A library of human transcription factor genes is screened for differentiation of human pluripotent stem cells.

DOI: 10.1038/s41587-020-0742-6

Source: https://www.nature.com/articles/s41587-020-0742-6