Methods of generating spinal cord glutamatergic interneurons (V2a interneurons) from human pluripotent stem cells (hPSCs) are provided. A method of the present disclosure may include culturing a first population of hPSCs in vitro in a neural induction medium that includes: a retinoic acid signaling pathway activator; a sonic hedgehog (Shh) signaling pathway activator; and a Notch signaling pathway inhibitor, wherein the culturing results in generation of a second population of cultured cells containing CHX10+ V2a interneurons. Also provided are non-human animal models that include the hPSC-derived spinal cord glutamatergic interneurons, and methods of producing the non-human animal models.

The present invention relates generally to the field of cell biology of stem cells, more specifically the directed differentiation of pluripotent or multipotent stem cells, including human embryonic stem cells (hESC), somatic stem cells, and induced human pluripotent stem cells (hiPSC) using novel culture conditions. Specifically, methods are provided for obtaining neural tissue, floor plate cells, and placode including induction of neural plate development in hESCs for obtaining midbrain dopamine (DA) neurons, motor neurons, and sensory neurons. Further, neural plate tissue obtained using methods of the present inventions are contemplated for use in co-cultures with other tissues as inducers for shifting differentiation pathways, i.e. patterning.

The invention provides a method for producing a cell aggregate containing a ciliary marginal zone-like structure by culturing a cell aggregate containing a retinal tissue in which Chx10 positive cells are present in a proportion of 20% or more of the tissue in a serum-free medium or serum-containing medium, each containing a substance acting on the Wnt signal pathway for only a period before the appearance of a RPE65 gene expressing cell, followed by culturing the “cell aggregate in which a RPE65 gene expressing cell does not appear” thus obtained in a serum-free medium or serum-containing medium, each not containing a substance acting on the Wnt signal pathway and so on.

This invention provides improved methods for generation of hematopoietic precursor cells from a pluripotent stem cell and hematopoietic precursor cells generated thereof. The hematopoietic precursor cells express CXCR4 or runx1c and are capable of homing and/or engraftment in bone marrow.

The present invention relates to a novel process of producing therapeutic GMP grade Müller cells and Miller cells obtainable therefrom, derived from stem cells using products that are free of animal-derived components. The Müller cells are suitable for treatment of eye disease, including glaucoma. There is also provided a cell culture medium.

The present invention provides methods to promote the differentiation of pluripotent stem cells and the products related to or resulting from such methods. In particular, the present invention provides an improved method for the formation of pancreatic hormone expressing cells and pancreatic hormone secreting cells. In addition, the present invention also provides methods to promote the differentiation of pluripotent stem cells without the use of a feeder cell layer and the products related to or resulting from such methods. The present invention also provides methods to promote glucose-stimulated insulin secretion in insulin-producing cells derived from pluripotent stem cells.

The present disclosure provides methods of lineage specific differentiation of pluripotent stem cells, including induced pluripotent stem cells, into floor plate midbrain progenitor cells, determined dopamine (DA) neuron progenitor cells, and/or DA neurons. Also provided are compositions uses thereof, such as for treating neurodegenerative diseases and conditions, including Parkinson's disease.

Disclosed herein are cell cultures comprising dorsal and/or ventral PDX1-positive foregut endoderm cells and methods of producing the same. Also disclosed herein are cell populations comprising substantially purified dorsal and/or ventral PDX1-positive foregut endoderm cells as well as methods for enriching, isolating and purifying dorsal and/or ventral PDX1-positive foregut endoderm cells from other cell types. Methods of identifying differentiation factors capable of promoting the differentiation of dorsal and/or ventral PDX1-positive foregut endoderm cells, are also disclosed.

Provided is a method of inducing oligodendrocyte precursor cells (OPCs) through direct reprogramming from human somatic cells into which a nucleic acid molecule encoding an Oct4 protein or Oct4 protein-treated human somatic cells. The method of inducing OPCs by treating Oct4-overexpressing human somatic cells with a low molecular weight substance may establish OPCs with high efficiency in a short period of time through direct reprogramming without via neural stem cells, and thus the OPCs are useful as a cell therapeutic agent for an intractable demyelinating disease.

Embodiments herein relate to in vitro production methods of hematopoietic stem cell (HSC) and hematopoietic stem and progenitor cell (HSPC) that have long-term multilineage hematopoiesis potentials upon in vivo engraftment. The HSC and HSPCs are derived from pluripotent stem cells-derived hemogenic endothelia cells (HE) by non-integrative episomal vectors-based gene transfer.