Abstract: Methods of tissue engineering, and more particularly methods and compositions for generating various vascularized 3D tissues, such as 3D vascularized embryoid bodies and organoids are described. Certain embodiments relate to a method of generating functional human tissue, the method comprising embedding an embryoid body or organoid in a tissue construct comprising a first vascular network and a second vascular network, each vascular network comprising one or more interconnected vascular channels; exposing the embryoid body or organoid to one or more biological agents, a biological agent gradient, a pressure, and/or an oxygen tension gradient, thereby inducing angiogenesis of capillary vessels to and/or from the embryoid body or organoid; and vascularizing the embryoid body or organoid, the capillary vessels connecting the first vascular network to the second vascular network, thereby creating a single vascular network and a perfusable tissue structure.

Abstract: Forced expression of a handful of transcription factors (TFs) can induce conversions between cell identities; however, the extent to which TFs can alter cell identity has not been systematically assessed. Here, we assembled a human TFome, a comprehensive expression library of 1,578 human TF clones with full coverage of the major TF families. By systematically screening the human TFome, we identified 77 individual TFs that induce loss of human-induced-pluripotent-stem-cell (hiPSC) identity, suggesting a pervasive ability for TFs to alter cell identity. Using large-scale computational cell type classification trained on thousands of tissue expression profiles, we identified cell types generated by these TFs with high efficiency and speed, without additional selections or mechanical perturbations. TF expression in adult human tissues only correlated with some of the cell lineage generated, suggesting more complexity than observation studies can explain.

Abstract: Methods of tissue engineering, and more particularly methods and compositions for generating various vascularized 3D tissues, such as 3D vascularized embryoid bodies and organoids are described. Certain embodiments relate to a method of generating functional human tissue, the method comprising embedding an embryoid body or organoid in a tissue construct comprising a first vascular network and a second vascular network, each vascular network comprising one or more interconnected vascular channels; exposing the embryoid body or organoid to one or more biological agents, a biological agent gradient, a pressure, and/or an oxygen tension gradient, thereby inducing angiogenesis of capillary vessels to and/or from the embryoid body or organoid; and vascularizing the embryoid body or organoid, the capillary vessels connecting the first vascular network to the second vascular network, thereby creating a single vascular network and a perfusable tissue structure.