The electrical pacemakers currently being used for the therapeutic approaches for treatment of sick sinus syndrome are not hormonally regulatable and entail risks through infections or premature battery discharge. These problems could be overcome by means of biological cardiac pacemakers obtained from pluripotent stem cells (PSCs). It has been shown that the controlled differentiation of stem cells with TBX, inductors of sinoatrial node cells, and an additional Myh6 promoter-specific antibiotic selection can give cardiomyocyte aggregates consisting to an extent of more than 80% of physiologically functional pacemaker cells. These induced sinoatrial bodies (iSABs) for the first time exhibited very high beat frequencies (300-400 bpm), similar to those in a murine heart, and were able to stably rhythmically stimulate heart muscle cells ex vivo. In the iSAB transcriptome decoded by means of RNA-seq, it was possible to assign almost all the genes to the ontologies of heart function/heart development and the structures of contractile cells. Overall, this is the first example of a high-purity functional sinoatrial tissue derived from stem cells, which means that a crucial step for future cell therapy and the testing of medicaments in vitro is being implemented.

Methods of producing synthetic corneas are disclosed which are differentiated from retinal stem cells (rSC) derived from parthenogenetically activated human oocytes, including that such synthetic corneas are produced in the absence of a 3-D scaffold. Isolated synthetic corneas, produced by the disclosed methods, are also described.

The present teachings provide for a method of breeding livestock in vitro. Provided are steps to create embryonic stem cells from a plurality of blastocysts, genotype the embryonic stem cells to select the best embryos for mating to create offspring, and induce the embryonic stem cells into primordial germ cell-like cells (PGCLCs). Male PGCLCs are further induced into spermatogonial stem cell-like cells, and then spermatid-like cells. Female PGCLCs are induced into oocytes, which are then matured. The resulting gametes can then be mixed with each other or with opposite sex gametes from animals with desirable genetics to create the next generation of embryos, which can then be run through the process again. This method of in vitro breeding can be used to increase the speed of genetic progress in livestock.

This disclosure provides ungulate embryonic stem cells (ESCs) derived from the inner cell mass of pre-implantation blastocysts or pluripotent cells from embryos. From an agricultural and biomedical perspectives, the derivation of stable ESCs from domestic ungulates is important for genomic testing and selection, genetic engineering, and providing an experimental tool for studying human diseases. Cattle are one of the most important domestic ungulates that are commonly used for food and bioreactors.

The invention relates to assays for screening growth factors, adhesion molecules, immunostimulatory molecules, extracellular matrix components and other materials, alone or in combination, simultaneously or temporally, for the ability to induce directed differentiation of pluripotent and multipotent stem cells.

Haploid human embryonic stem cells and cell lines, haploid multipotent human cells, and haploid differentiated human cells are provided. In addition, methods of making and using the haploid human cells are provided.

Methods of using a small molecule MYH11 agonist to inhibit intimal hyperplasia and to maintain a contractile phenotype in vitro and in vivo are described. Also described herein are methods for generating human contractile smooth muscle cells from human pluripotent stem cells under defined conditions in the presence of the small molecule MYH11 agonist.

A heart tissue model including a heart tissue with at least one inner cavity or a central chamber, wherein the heart tissue model including at least two different heart tissues selected from left ventricle tissue, right ventricle tissue, atrial tissue, outflow tract tissue, atrioventricular canal tissue, sinoatrial node tissue, and atrioventricular node tissue, wherein the central chamber can be shared by at least two different heart tissues, and wherein the at least two different heart tissues include a calcium signaling connection and/or ability to propagate a tissue contraction-; methods of generating such a tissue model and uses of the tissue model for screening purposes is disclosed.

Provided is a method for obtaining the germ cell lineage of an oviparous vertebrate more efficiently than conventional techniques. A host oviparous vertebrate is prepared at a developmental stage after the development of black pigmentary cells in the retina and before the formation of multiple layers of germ cells in the genitals, and isolated undifferentiated germ cells from a donor oviparous vertebrate are transplanted into the host oviparous vertebrate.

Methods of using a small molecule MYH11 agonist to inhibit intimal hyperplasia and to maintain a contractile phenotype in vitro and in vivo are described. Also described herein are methods for generating human contractile smooth muscle cells from human pluripotent stem cells under defined conditions in the presence of the small molecule MYH11 agonist.