Harvard Medicine has successfully leveraged a range of products from Signosis for their study on the programming landscape mediated by transcription factors (TFs) in human pluripotent stem cells (hPSCs). The study utilized the Transcriptional Interaction TF Plate Array I, Combo TF Activation Profiling Plate Array with Nuclear Extraction Kit, Promoter-Binding TF Profiling Assay I, TF Activation Profiling Plate Array II with Nuclear Extraction Kit, and Nuclear Extraction Kit to screen a comprehensive library containing 1,564 TF genes and 1,732 TF splice isoforms in three hPSC lines.
The study discovered 290 TFs, including 241 that were previously unreported, that induce differentiation in 4 days without alteration of external soluble or biomechanical cues. Using four of the hits, they were able to program hPSCs into neurons, fibroblasts, oligodendrocytes, and vascular endothelial-like cells that have molecular and functional similarity to primary cells. The cell-autonomous approach enabled parallel programming of hPSCs into multiple cell types simultaneously.
The study demonstrated the potential for large-scale combinatorial screening of the Human TFome to complement other strategies for cell engineering based on developmental biology and computational systems biology. The Signosis products proved to be valuable tools in the screening process and contributed to the success of the study.
Alex H. M. Ng1,2,3,14, Parastoo Khoshakhlagh1,2,3,14, Jesus Eduardo Rojo Arias 4,13, Giovanni Pasquini4, Kai Wang 5,6, Anka Swiersy4, Seth L. Shipman7 , Evan Appleton 1,2,3, Kiavash Kiaee1,2,3, Richie E. Kohman1,2, Andyna Vernet2 , Matthew Dysart1,2, Kathleen Leeper 1,2, Wren Saylor 1,2, Jeremy Y. Huang 1,2, Amanda Graveline2 , Jussi Taipale8,9,10, David E. Hill 1,11, Marc Vidal1,11, Juan M. Melero-Martin5,6, Volker Busskamp 4,12 ✉ and George M. Church 1,2,3 ✉
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.