A comprehensive library of human transcription factors for cell fate engineering (scRNA-Seq)

Human pluripotent stem cell (hPSC)-derived cells offer an unprecedented opportunity to model diverse human tissue functions. However, the field lacks a generalized approach to rapidly and efficiently generate individual cell types of interest and to incorporate them into complex but defined tissues. To systematically explore the transcription factor (TF)-mediated hPSC programming landscape, we constructed the Human TFome: a comprehensive human TF library containing 1,564 TF (1,732 splice-isoforms). We discovered 241 previously unreported factors that individually converted hPSCs into diverse lineages with up to 99% efficiency in four days without alteration of external factors. Among these, we programmed neurons, fibroblasts, oligodendrocytes and endothelial cells that have molecular, transcriptomic and functional similarity to primary cells. Splice-isoform-specificity doubled endothelial conversion efficiency into in vivo-functional cells. Our cell-autonomous approach enabled parallel and orthogonal hPSCs programming into multiple cell types simultaneously without altering any microenvironmental cues. We generated in vivo-engraftable induced oligodendrocytes that expedited myelination within synthetically accelerated cerebral organoids.

搜集汇总

背景与挑战

背景概述

该数据集基于单细胞RNA测序（scRNA-Seq），提供了一个全面的人类转录因子库（Human TFome），包含1,564个转录因子（1,732个剪接异构体），用于高效编程人类多能干细胞（hPSCs）生成多种细胞谱系（如神经元、成纤维细胞等），在4天内转换效率高达99%，且无需外部因素干预。其特点包括剪接异构体特异性增强细胞功能、细胞自主编程支持并行生成多种细胞类型，以及应用于加速脑类器官髓鞘形成等组织工程。