Iterative transcription factor screening enables rapid generation of microglia-like cells from human iPSC

• DOI: 10.1101/2022.06.03.494617
• Publication Date: 2023-04-04T17:35:59Z
• Authors: Songlei Liu; Li Li; Fan Zhang; Björn van Sambeek; Evan Appleton; Alex H. M. Ng; Parastoo Khoshakh...; Yuting Chen; Mariana Garcia-Co...; Chun-Ting Wu; Jeremy Y. Huang; Yuqi Tan; George Chao; John Aach; Jenny Tam; Elaine T. Lim; Soumya Raychaudhuri; George M. Church
• Keywords: Cell type

Abstract The ability to differentiate stem cells into human cell types is essential define basic mechanisms and therapeutics, especially for not routinely accessible by biopsies. But while engineered expression of transcription factors (TFs) identified through TF screens has been found rapidly efficiently produce some types, generation other that require complex combinations TFs elusive. Here we develop an iterative, pooled single-cell screening method improves the identification effective using microglia-like as a testbed: Two iterations combination SPI1, CEBPA, FLI1, MEF2C, CEBPB, IRF8 sufficient iPSC in 4 days. Characterization TF-induced microglia demonstrated molecular functional similarity primary microglia. We explore use atlas reference datasets confirm how combining perturbation gene data can enable construction causal regulatory networks. describe what will be needed fashion these methods generalized integrated pipeline, further ideas enhancement, possible applications.