The present invention relates to methods for deriving multipotent Isl1+ cells (i.e. methods for inducing a cell to enter a multipotent Isl1+ lineage), methods for differentiating Isl1+ cells to cardiac cells, cells obtainable by such methods, kits and compositions for carrying out the methods in accordance with the invention, and also medical applications and pharmaceutical compositions of said cells.

Provided herein are methods for the differentiation of pluripotent stem cells to committed cardiac progenitor cells. Further provided herein are methods for the use of the committed cardiac progenitor cells in the treatment of cardiac disorders.

Disclosed are methods for preparing retinal pigment epithelium (RPE) cells from pluripotent stem cells (PSCs). More particularly, it represents an automated method that combines in a sequential manner three differentiating agents to direct the differentiation of human PSCs into RPE cells.

The present invention relates to improvement of the yield of skin-derived pluripotent precursor cells in induction of differentiation of stem cells to skin-derived pluripotent precursor cells. The present invention provides a method for preparing skin-derived pluripotent precursor cell comprising culturing a neural crest stem cells in the presence of at least one selected from the group consisting of laminin and a fragment thereof to differentiate the cells to skin-derived pluripotent precursor cells, wherein the laminin is at least one selected from the group consisting of laminin 111, laminin 121, laminin 332, laminin 421, laminin 511, laminin 521, and a variant thereof.

The present invention relates to, inter alia, an engineered cell (e.g., iPSC, IPS-derived NK, or NK cell) comprising a disrupted B2M gene and an inserted polynucleotide encoding one or more of SERPINB9, a fusion of IL15 and IL15Rα, and/or HLA-E. The engineered cell can further comprise a disrupted CIITA gene and an inserted polynucleotide encoding a CAR, wherein the CAR can be an anti-BCMA CAR or an anti-CD30 CAR. The engineered cell may further comprise a disrupted ADAM17 gene, a disrupted FAS gene, a disrupted CISH gene, and/or a disrupted REGNASE-1 gene. Methods for producing the engineered cells are also provided, and therapeutic uses of the engineered cells are also described. Guide RNA sequences targeting described target sequences are also described.

The present invention provides a method for producing a retinal progenitor cell, including (1) a first step of subjecting pluripotent stem cells to floating culture in a serum-free medium to form an aggregate of pluripotent stem cells, and (2) a second step of subjecting the aggregate formed in step (1) to floating culture in a serum-free medium or serum-containing medium each being free of a substance acting on the Sonic hedgehog signal transduction pathway but containing a substance acting on the BMP signal transduction pathway, thereby obtaining an aggregate containing retinal progenitor cells.

The present invention provides a method for producing dopaminergic neuron progenitor cells from pluripotent stem cells, which method comprises the steps of: (i) performing adherent culture of pluripotent stem cells on an extracellular matrix in a medium containing a reagent(s) selected from the group consisting of BMP inhibitor, TGFβ inhibitor, SHH signal-stimulating agent, FGF8, and GSK3β inhibitor; (ii) collecting Corin- and/or Lrtm1-positive cells from the cells obtained in Step (i) using a substance which binds to Corin and/or a substance which binds to Lrtm1; and (iii) performing suspension culture of the cells obtained in Step (ii) in a medium containing a neurotrophic factor.

An object of the present invention is to provide a method of producing an intestinal epithelial cell, which has a large number of cells per area and a high accuracy of kinetic prediction for a CYP3A4 substrate drug such as midazolam, by inducing the differentiation of a pluripotent stem cell, as well as the intestinal epithelial cell, a cell sheet, an evaluation method for a test substance, a screening kit for a test substance, and a cell preparation. According to the present invention, there is provided a production method for an intestinal epithelial cell, including a first differentiation step of differentiating a pluripotent stem cell into an intestinal stem cell, a proliferation step of proliferating the intestinal stem cell obtained in the differentiation step, and a second differentiation step of differentiating the intestinal stem cell obtained in the proliferation step into an intestinal epithelial cell, in which the proliferation step is a step of bringing the intestinal stem cell into a specific state.

Culture media capable of promoting differentiation of pluripotent stem cells (PSCs) into mesenchymal stem cells (MSCs) or supporting expansion of MSCs is provided. Methods of differentiation of PSCs into MSCs are provided. Methods of expanding MSCs without differentiation are also provided.

The invention provides culture platforms, cell media, and methods of differentiating pluriptent cells into hematopoietic cells. The invention further provides pluripotent stem cell-derived hematopoietic cells generated using the culture platforms and methods disclosed herein, which enable feed-free, monolayer culturing and in the absence of EB formation. Specifically, pluripotent stem cell-derived hematopoietic cell of this invention include, and not limited to, iHSC, definitive hemogenic endothelium, hematopoietic multipotent progenitors, T cell progenitors, NK cell progenitors, T cells, and NK cells.