The present invention provides a cell culture for obtaining an epithelial organoid, the cell culture comprising i) epithelial stem cells, or tissue fragments comprising said epithelial stem cells, ii) a basal medium for animal or human cells, iii) a Bone Morphogenetic Protein (BMP) inhibitor, iv) a mitogenic growth factor selected from the group consisting of epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha), basic fibroblast growth factor (bFGF), brain-derived neurotrophic factor (BDNF) and keratinocyte growth factor (KGF), v) at least one soluble culture enhancer, wherein said at least one culture enhancer induces correct polarization of the cells in said cell culture within the developing organoid such as a laminin/entactin complex or entactin, and vi) a Wnt agonist if said epithelial stem cells, or tissue fragments comprising said epithelial stem cells are healthy cells, wherein said at least one soluble culture enhancer in said cell culture is a laminin/entactin complex in a concentration between 0.2 mg/ml and 3.4 mg/ml. A cell culture medium, an in-vitro method for obtaining an epithelial organoid, and an epithelial organoid obtained by said method are also disclosed.

A method for producing astrocytes includes a step of dissociating an embryoid body into single cells and suspension-culturing the cells in a serum-free medium containing basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) to obtain a neural stem cell mass, and a step of dissociating the neural stem cell mass into single cells and adhesion-culturing the cells in a serum-free medium to obtain a cell population containing astrocytes.

In some aspects, disclosed herein are methods and compositions for treatment of Parkinson's disease using fibroblasts or cells derived from fibroblasts. Also disclosed herein are methods and compositions for generating dopaminergic cells from fibroblasts. Dopaminergic cells generated from fibroblasts are described. Methods of the present disclosure include methods for treatment or preventing of Parkinson's disease comprising the use of fibroblasts or dopaminergic cells generated from fibroblasts.

The present invention relates to a method for efficiently differentiating neural stem cells into astrocytes and, more particularly, to a cell conversion-based method for more efficiently differentiating human neural stem cells into astrocytes that exhibit immune response suppression ability within a short period of time. Unlike a conventional method, the method for differentiating neural stem cells into astrocytes by using a differentiation medium containing a combination of several cytokines, according to the present invention, involves a shortened differentiation time and has excellent differentiation efficiency, and the differentiated astrocytes exhibit immune response suppression ability, and thus can be useful as an agent for treating various brain diseases such as degenerative neurological diseases.

The present invention relates to oligonucleotides that are capable of inducing expression of ubiquitin-protein ligase E3A (UBE3A) from the paternal allele in animal or human neurons. The oligonucleotides target the suppressor of the UBE3A paternal allele by hybridization to SNHG14 long non-coding RNA downstream of SNORD109B. The present invention further relates to pharmaceutical compositions and methods for treatment of Angelman syndrome.

Enhanced methods for the generation of medial ganglionic eminence (MGE) cells from pluripotent stem cells are provided that involve an additional step of contacting the cells with an activator of FGF8 signaling while differentiating Pax6+ cells progenitor cells into MGE cells with an activator of sonic hedgehog, and optionally a Wnt inhibitor. The activator of FGF8 signaling shifts the differentiation of the population of cells to NKX2.1+ MGE cells, rather than to CopuTFII+ caudal ganglionic eminence (CGE) cells. Methods for treatment of neurological disorders, such as epilepsy, by transplant of MGE cells, or GABAergic interneurons derived from human pluripotent stem cells, into a subject in need of treatment are also provided. Human pluripotent stem cell derived MGE cells when transplanted successfully suppress spontaneous seizures, e.g. in epilepsy. We also have developed a method to purify MGE cells and maturing interneurons from differentiated pluripotent stem cells using cell surface marker and molecular beacon technology.

Human pluripotent stem cells are differentiated in vitro into oligodendro-spheroids comprising oligodendrocytes for use in analysis, screening programs, and the like.

Provided is a method for inducing differentiation of neural crest cells into neurons of the autonomic nervous system, the method including the step of culturing neural crest cells in the presence of at least one of a BMP signaling pathway activator, an SHH signaling pathway inhibitor, and a Wnt signaling pathway inhibitor.

A population of enteroendocrine cells (EEC) is obtained from a mammalian post-natal cell population, such as a population including post-natal stem cells, by treating the population with a plurality of small molecules that upregulate ChgA and promote differentiation of the cells to form the enteroendocrine cells. The upregulation of ChgA is such that the fraction of cells expressing CGA in the obtained cell population, as measured by a ChgA Immunostaining Assay, is at least about 1.5%. Small molecules that can be used to differentiate the post-natal cells into the enteroendocrine cells can include at least one of a Wnt activator, a Notch inhibitor, a Wnt inhibitor, a MEK/ERK inhibitor, a growth factor, a HDAC inhibitor, a Histone Methylation Inhibitor, a Tgf-β inhibitor, and a NeuroD1 activator. Also, the insulin expression of a population of mammalian cells is increased by treating the population with a plurality of small molecules that increase the insulin expression.

A method for easily and efficiently preparing a functional and matured neuromuscular junction (NMJ) in vitro includes producing an artificial neuromuscular junction by transiently expressing MyoD in pluripotent stem cells to induce myogenic differentiation, and culturing the cells obtained by transiently expressing MyoD in pluripotent stem cells to induce myogenic differentiation in a medium containing a neurotrophic factor to induce neuronal differentiation.