Similar Datasets
Project description: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.
| S-EPMC7610615 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2013-08-04 | E-GEOD-46855 | biostudies-arrayexpress
Project description: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.
2020-10-22 | GSE159784 | GEO
Project description: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.
2020-10-22 | GSE159779 | GEO
Project description: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.
2020-10-22 | GSE159778 | GEO
Project description: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.
2020-10-22 | GSE159783 | GEO
Project description: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.
2020-10-22 | GSE159781 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2024-06-24 | GSE243517 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2018-01-31 | GSE103470 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2015-11-04 | E-GEOD-74648 | biostudies-arrayexpress