Abstract: Compositions and methods disclosed concern an isogenic population of in vitro human embryonic stem cells comprising a disease form of the Huntingtin gene (HTT) at the endogenous HTT gene locus in the genome of the cell; wherein the disease form of the HTT gene comprises a polyQ repeat of at least 40 glutamines at the N-terminus of the Huntingtin protein (HTT). The cell lines of the disclosure comprise genetically-defined alterations made in the endogenous HTT gene that recapitulate Huntington's Disease in humans. Furthermore, the cell lines have isogenic controls that share a similar genetic background. Differentiating cell lines committed to a neuronal fate and fully differentiated cell lines are also provided and they also display phenotypic abnormalities associated with the length of the polyQ repeat of the HTT gene. These cell lines are used as screening tools in drug discovery and development to identify substances that fully or partially revert these phenotype abnormalities.

Abstract: The present disclosure relates to a neural ectodermal lineage cellular structure, and compositions and methods related thereto. In some embodiments, the disclosure provides a geometrically isolated neural ectodermal lineage cellular structure (neuruloid) including spatially segregated neuroepithelial cells, sensory placodes, neural crest cells, and epidermal cells having radial organization around a lumen within the neuroepithelial cells. The disclosure also provides methods directed to forming the neural ectodermal lineage cellular structure. The disclosure also provides methods and platforms directed to the neural ectodermal lineage cellular structure.

Abstract: Systems and methods for identifying molecules that are biologically active against a disease, where the method can comprise culturing a first mammalian cell population under organoid formation conditions in the presence of a test molecule to obtain a first organoid, wherein the first mammalian cell population, when cultured under the organoid formation conditions in the absence of the test molecule, results in an organoid with a disease phenotype; imaging the first organoid following exposure to the test molecule; analyzing one or more images of the first organoid using a neural network that has been trained to assign a probability score of disease or non-disease ranging between 0% and 100%; assigning the first organoid a probability score ranging between 0% and 100%; wherein the test molecule is biologically active against the disease if the probability score of the first organoid is greater than a cutoff probability score of non-disease or lower than a cutoff probability score of disease.

Abstract: Compositions and methods disclosed concern an isogenic population of in vitro human embryonic stem cells comprising a disease form of the Huntingtin gene (HTT) at the endogenous HTT gene locus in the genome of the cell; wherein the disease form of the HTT gene comprises a polyQ repeat of at least 40 glutamines at the N-terminus of the Huntingtin protein (HTT). The cell lines of the disclosure comprise genetically-defined alterations made in the endogenous HTT gene that recapitulate Huntington's Disease in humans. Furthermore, the cell lines have isogenic controls that share a similar genetic background. Differentiating cell lines committed to a neuronal fate and fully differentiated cell lines are also provided and they also display phenotypic abnormalities associated with the length of the polyQ repeat of the HTT gene. These cell lines are used as screening tools in drug discovery and development to identify substances that fully or partially revert these phenotype abnormalities.

Abstract: PiggyBac transposons and transposases with enhanced transposition activity in cells are provided. Also provided are associated methods and kits for both introducing exogenous DNA inserts into the genomes of host cells as well as for the removal of the inserts from the host cell genomes. Cells obtained by use of the compositions, methods and kits are also provided.

Abstract: PiggyBac transposons and transposases with enhanced transposition activity in cells are provided. Also provided are associated methods and kits for both introducing exogenous DNA inserts into the genomes of host cells as well as for the removal of the inserts from the host cell genomes. Cells obtained by use of the compositions, methods and kits are also provided.

Abstract: This invention features methods and compositions useful for treating and diseases caused by a dysregulation of the BMP/GDF branch of the TGF-? signaling pathway. Also disclosed are methods for identifying compounds useful for such therapy.

Abstract: The present invention relates to methods for maintaining the undifferentiated state of embryonic stem cells without the use of a feeder layer by activating the Wnt signal transduction pathway or by inhibiting glycogen synthase kinase-3 activity by contacting the cell with, inter alia, 6-bromoindirubin-3?-oxime. The present invention also relates to embryonic stem cell lines and cells derived therefrom that have been isolated and cultured in the absence of a feeder layer.

Abstract: The present invention provides methods of modulating TBF-?, particularly, nodal, Vg1 or BMP-2, but not activin, signalling by administration of a molecule that modulates the activity of TMEFF1. Diagnostic methods are also provided.

Abstract: This invention features methods and compositions useful for treating and diseases caused by a dysregulation of the BMP/GDF branch of the TGF-? signaling pathway. Also disclosed are methods for identifying compounds useful for such therapy.

Abstract: The present invention relates to methods for maintaining the undifferentiated state of embryonic stem cells without the use of a feeder layer by activating the Wnt signal transduction pathway or by inhibiting glycogen synthase kinase-3 activity by contacting the cell with, inter alia, 6-bromoindirubin-3?-oxime. The present invention also relates to embryonic stem cell lines and cells derived therefrom that have been isolated and cultured in the absence of a feeder layer.