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Provided is a method for obtaining a stem cell (for example, a mesenchymal stem cell or a hematopoietic stem cell) with an enhanced engraftment, clonogenic or migratory capacity comprising a step of co-culturing the said stem cell in contact with a NK cell activated with IL-15.

Provided is a method for differentiating cells comprising a step of contacting stem, progenitor or precursor cells with miR-130a to yield endothelial lineage cells.

Provided is a method for obtaining neural stem cells (NSCs) comprising steps of (i) culturing iPS cells in a medium containing an activin/TGF-β inhibitor, a canonical WNT activator, a BMP inhibitor, and a SHH activator, (ii) cultivating the cells obtained in (i) in a medium containing a canonical WNT activator, a SHH activator, and an antioxidant, and (iii) maintaining the cells obtained in (ii) in a medium containing a FGF activator, an EGF activator, and a LIF activator.  The obtained NSCs may be further differentiated into neurons or glial cells, preferably astrocytes.

Provided are a method for differentiating human iPSCs into Early Vascular Cells (EVCs) comprising steps of plating a single-cell suspension of the iPSCs onto a suitable surface and culturing the cells in a medium added with a ROCK inhibitor, and a method for generating a vascular network comprising the EVCs.

Provided is a composition comprising iPSC-derived endothelial cells (ECs) that overexpress Sirtuin 1 (SIRT1), wherein the iPSC-derived ECs comprise exogenous nucleic acid encoding SIRT1. SIRT1 is an NAD+ dependent deacetylase involved in the regulation of cell senescence. The said iPSC-derived ECs are expected to have stable endothelial phenotypes and cell proliferative capacities over time.

Provided is a method for generating induced notochordal cells (iNCs) from induced pluripotent stem cells (iPSCs) comprising steps of (i) to (iii) below, and a method for modulating intervertebral disc degeneration of a subject by administering the iNCs to the subject; (i)culturing the iPSCs in the presence of a GSK3 inhibitor to form primitive streak (PS) cells, (ii) contacting the PS cells with a vector encoding Brachyury, and (iii) expressing Brachyury in the PS cells; thereby inducing formation of iNCs.

Provided is a method for preparing an organotypic vascularized tissue, skin or mucosa equivalent from mammalian pluripotent stem cells comprising steps of i) culturing the stem cells under conditions to induce the formation of endothelial cells (SC-ECs), vascular smooth muscle cells/pericytes (SC-vSMCs), fibroblasts (SC-Fib) and keratinocytes (SC-KCs), ii) seeding the SC-ECs, SC-vSMCs and, optionally, SC-Fib obtained in step i) in or on a scaffold to induce formation of a vascularized dermal layer, and iii) seeding the SC-KCs obtained in step i) onto the vascularized dermal layer obtained in step ii) to induce the formation of a stratified layer of keratinized epidermis upon said vascularized dermal layer and provide an organotypic vascularized skin or mucosa equivalent.

Provided is a method for differentiating pluripotent cells into midbrain dopamine neurons comprising steps of (i) contacting a plurality of pluripotent cells with a TGFp/Activin-Nodal signaling inhibitor, a Sonic hedgehog signaling activator, and a Wnt signaling activator at incrementing concentrations such that a plurality of the cells differentiate and express FOXA2 and LMX1A, and (ii) subjecting the differentiated cells to conditions favoring maturation of the cells into dopamine neurons, for example, contacting the cells with BDNF, GDNF, cAMP, TGFP3, ascorbic acid, and/or DAP; thereby differentiating them into midbrain dopamine neurons.

Provided is a culture medium and a method of differentiating a pluripotent stem cell into a microglial cell by using the culture medium, wherein the culture medium comprises amino acids, vitamins, inorganic salts, glucose or galactose, buffering agent, serum albumin, transferrin, sodium chloride, a pyruvate salt, glutamine, biotin, ascorbic acid, and lactic acid, and the osmolality of the culture medium is at least 275 mOsm. The culture medium may further comprise corticosterone, linoleic acid, linolenic acid, progesterone, tocopherol, lipoic acid, L-carnitine, ethanolamine, D-galactose, putrescine dihydrochloride, sodium selenite, BSA, catalase, glutathione, insulin, human-holo-transferrin, superoxide dismutase, and T3.

Provided is a method of nuclear reprogramming of a mammalian somatic cell to an iPS cell, comprising a step of contacting the mammalian somatic cell with a synthetic transcription factor that activates expression of a pluripotency factor gene (oct3/4, sox2, klf4, c-myc, lin28, nanog, glis-1, hcI2, and bclx), wherein the synthetic transcription factor comprises (i) at least one guide RNA comprising a DNA-binding segment to a promoter region of the pluripotency factor gene, and a polypeptide-binding segment, and (ii) at least one transcriptional modulator which binds said polypeptide-binding segment of said guide RNA. In a preferred embodiment, the said transcriptional modulator comprises an enzymatically inactive Cas9 polypeptide (dCas9) which is fused to a transcriptional activation domain VP64 or p65.

Provided is a method for promoting maturation of mammalian hepatocytes including human iPS cell-derived hepatocytes, comprising a step of exposing said hepatocytes to at least one maturation factor selected from the group consisting of Src kinase inhibitors, vitamin D derivatives, hypoxia inducing compounds, sphingosine derivatives, PPARs activators, PAF, PKC inhibitors, and combinations thereof.

Provided is a method for producing a cell population enriched for CLEC9A+ dendritic cells comprising a step of culturing stem cells in a cell culture comprising a notch ligand, SCF, FLT3L, TPO, and IL-3 and/or GMCSF.

Provided is a method for engineering three-dimensional functional adult cardiac tissue from iPS cell-derived cardiomyocytes comprising a step of electromechanically conditioning the derived cardiomyocytes, wherein the electromechanical conditioning includes a step of exposing the derived cardiomyocytes to electromechanical stimuli that increases in intensity over a period of time.

Provided is a method for generating an iPS cell with an increased efficiency of induction, comprising a step of introducing to an animal somatic cell at least one nuclear reprogramming inducing factor and a BRD3R polypeptide, or at least one nucleic acid sequence expressing the at least one nuclear reprogramming factor and the BRD3R-related polypeptide.

Provided is a method for deriving a naive pluripotent stem cell comprising a step of culturing a primed pluripotent stem cell in a culture medium containing an effective amount of a lysophosphatidic acid receptor (LPAR) agonist, thereby reverting the primed pluripotent stem cell to a naive pluripotent stem cell.

Provided is a method for generating an otic progenitor cell from an iPSC comprising steps of i) culturing an iPSC under conditions sufficient to inhibit Wnt signaling and activate FGF signaling for a first time period sufficient to induce upregulation of one or more otic cell markers, and ii) culturing the cell obtained in step i) under conditions sufficient to activate Wnt signaling and reduce FGF signaling relative to step i) for a second time period sufficient to maintain upregulated expression of said one or more otic cell markers.

Provided is a method for proliferating epithelial cells in an originating epithelial cell population derived from iPSCs under feeder-cell free expansion culture conditions, wherein the expansion culture conditions comprise an agent that activates telomerase reverse transcriptase and/or inhibits TGF-beta signaling in the population.

Provided is a dendritic cell derived from a pluripotent stem cell, which is stably modified with a nucleic acid molecule encoding an antigen or one or more immunogenic epitopes wherein the dendritic cell expresses and presents the antigen or the epitope(s) thereof.

Provided is a method for differentiating cells into insulin-producing βcells, comprising steps of i) providing a pancreatic progenitor cell population comprising at least one cell capable of differentiation and ii) incubating said cell population in the presence of a Yap1 inhibitor; thereby obtaining a cell population enriched for insulin-producing βcells; wherein the said cell capable of differentiation is a human iPS cell.

Provided is a method for producing satellite cells or satellite-like cells expressing CD56/Pax3, CD56Pax7, and/or Pax3/Pax7, comprising a step of contacting a pluripotent stem cell with one or more compounds including a TGF-β receptor inhibitor or a wnt pathway activator.

Provided is a telomerase null pluripotent stem cell comprising two mutated alleles of a telomerase activity gene selected from the group comprising hTERT gene and hTER gene wherein the said alleles comprise an introduced and removable portion of said hTERT or hTER gene.

Provided is a method for enhancing differentiation of multipotent stem cells and pluripotent stem cells into neurons comprising steps of seeding the cells onto a substrate patterned with nano- and/or micro-grating structures, wherein the nano- and/or micro-grating structures are selected from gratings and hierarchical gratings, wherein said hierarchical gratings comprise said gratings with secondary structures at the base of and within the grooves of said gratings, and contacting the cells with medium. In a preferred embodiment, the differentiated neurons are dopaminergic neurons.

Provided is a method for selecting a mammalian induced pluripotent stem cell progenitor comprising a step of isolating an induced pluripotent stem cell progenitor expressing one or more of Oct4, Sox2, Klf4 and cMyc, and having increased expression of an estrogen related receptor relative to a reference cell, thereby selecting an induced pluripotent stem cell progenitor which generates an iPSC at high efficiency.

The present invention relates to a method for reprogramming a human somatic cell into a human iPS cell by using a specific combination of small-molecule compounds comprising a step of culturing said somatic cell in the presence of at least a combination of a DNA methyltransferase (DNMT) inhibitor, a Sirtuin inhibitor and a poly (ADP-ribose) polymerase (PARP) inhibitor.

Provided is a method for producing compositions comprising a population of cardiomyocytes enriched for or substantially devoid of sinoatrial node-like pacemaker cardiomyocytes (SANLCM) from human pluripotent stem cells.

The present invention relates to a reprogramming method for producing iPSC by transducing somatic differentiated cells with a viral vector expressing Δ133p53β isoform, Δ133p53γ isoform or both of Δ133p53β and Δ133p53γ isoforms in the absence of induction of any Yamanaka transcription factors or without depleting or inducing mutations in p53 genes.

Provided is a method for differentiating pluripotent stem cells to hematopoietic lineage cells through hemogenic endothelium (HE) under feeder free conditions without EB formation, wherein the provided hematopoietic lineage cells comprise hematopoietic stem cells (HSC), hematopoietic multipotent progenitor cells (MPP), pre-T cell progenitor cells, pre-NK cell progenitor cells, T cell progenitor cells, NK cell progenitor cells, T cells, NK cells, NKT cells, or B cells.

Provided is a method for producing a cell exhibiting one or more chronological marker comprising a step of reducing the level of genomic nucleic acid methylation in a cell that is deficient in the said chronological marker, especially wherein the said cell is a somatic cell differentiated from an iPS cell. In some embodiments, reducing the level of genomic nucleic acid methylation in the cell induces one or more chronological marker to establish a disease model of a late-onset disease.

Provided is a method of producing primitive like macrophages from stem cells, a kit used in the method, and uses of the primitive like macrophage for in-vitro disease models and drug screening for a neurodegenerative disease and so on.

Provided is a method of identifying differentiation markers, comprising steps of a) culturing a primary cell under conditions such that said primary cell de-differentiates to generate an iPSC, b) treating said iPSC under conditions such that said iPSC differentiates into a differentiated cell, and c) identifying molecular markers that are indicative of differentiation into said differentiated cell. In some preferred embodiments, the differentiated cells are pancreatic beta cells and markers of differentiation are identified and validated.