A production method for a cerebral organoid having amyloid plaques is provided, the method including a step (a) of forming, in the presence of a SMAD inhibitor, an embryoid body from a pluripotent stem cell having a mutation in an Alzheimer's disease-related gene; a step (b) of embedding the embryoid body after the step (a) in an extracellular matrix and three-dimensionally culturing the embedded embryoid body in the presence of a SMAD inhibitor and a glycogen synthase kinase 3β (GSK3β) inhibitor to form an organoid; and a step (c) of removing the organoid after the step (b) from the extracellular matrix and subjecting the removed organoid to stirring culture in a medium, where at least a part of the step (c) is carried out in the presence of leukemia inhibitory factor (LIF).

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.

Methods are provided for the production of photoreceptor cells and photoreceptor progenitor cells from pluripotent stem cells. Additionally provided are compositions of photoreceptor cells and photoreceptor cells, as well as methods for the therapeutic use thereof. Exemplary methods may produce substantially pure cultures of photoreceptor cells and/or photoreceptor cells.

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.

Provided herein are compositions and methods for generation of naive human pluripotent stem cells. The method comprises incubation of iPSCs under 5% O.sub.2 in a medium comprising 5% glucose, an MEK inhibitor, a GSK3β inhibitor, human leukemia inhibitory factor (LIF), human insulin and Torin 1. The method does not need any other inhibitors or transgene expression. The naive human pluripotent cells can be used to generate a large amount of mature human cells from all three germ layers in host non-human animals.

The method for producing a cell aggregate including glial progenitor cells according to the present invention comprises: (1) a step of subjecting pluripotent stem cells to suspension culture in an embryoid-body-forming culture medium containing one or more SMAD signaling inhibitors and one or more Wnt signaling activators in the absence of feeder cells for 5 days to 10 days, to form a cell aggregate; (2) a step of subjecting the cell aggregate obtained in (1) to suspension culture in an embryoid-body-forming culture medium containing retinoic acid; (3) a step of subjecting the cell aggregate obtained in (2) to suspension culture in an embryoid-body-forming culture medium or neuron-and-glia-proliferating culture medium containing retinoic acid and one or more SHH signaling activators; and (4) a step of subjecting the cell aggregate obtained in (3) to suspension culture in a neuron-and-glia-proliferating culture medium containing no retinoic acid and one or more SHH signaling activators.

Methods are provided for the efficient differentiation of hPSCs into HSC-like cells and endothelial cells in defined, monolayer conditions solely using extracellular signals to guide differentiation. The instant disclosure also provides methods of screening for cellular responses of the generated hematopoietic stem cells, endothelial cells and derivatives thereof. Treatment methods making use of the generated hematopoietic stem cells and endothelial cells are also provided. The instant disclosure also provides systems, compositions, and kits for practicing the methods of the disclosure.

A method for inducing immature oocytes includes introducing four genes consisting of FIGLA, NOBOX, LHX8 and TBPL2, or transcripts or expressed proteins thereof, into at least one type of cell selected from the group consisting of pluripotent stem cells, epiblast-like cells and primordial germ cells. A method for producing mature oocytes includes introducing four genes consisting of FIGLA, NOBOX, LHX8 and TBPL2, or transcripts or expressed proteins thereof, into at least one type of cell selected from the group consisting of pluripotent stem cells, epiblast-like cells and primordial germ cells, and co-culturing the cell obtained after the introduction and ovarian somatic cells.

The present invention discloses a method for screening, activating, amplifying and cryopreserving mesenchymal stem cells in vitro and establishing a cell bank of mesenchymal stem cells. The method includes the following steps: using a dedicated primary screening medium of mesenchymal stem cells for first-stage screening culture to obtain purified mesenchymal stem cells; using a dedicated activation and amplification medium of mesenchymal stem cells to perform second-stage activation and large-scale amplification culture on the purified mesenchymal stem cells to obtain a large number of mesenchymal stem cells with activation functions; using a dedicated cryopreserving fluid of mesenchymal stem cells to cryopreserve the stem cells and performing preservation according to ABO/RH typing and HLA typing; and establishing an information file for retrieval to construct a mesenchymal stem cell bank.

Among the various aspects of the present disclosure is the provision of engineered cells, animal models, and uses thereof for modeling low grade glioma (LGG). An aspect of the present disclosure provides for a population of cells engineered to silence, downregulate, knock out, or reduce or knock down Cxcl10 expression. Another aspect of the present disclosure provides for an animal engineered to be deficient in Cxcl10, downregulate or reduce expression of Cxcl10, knock out Cxcl10, or knock down Cxcl10 (e.g., Cxcl10.sup.−/− mice). Yet another aspect of the present disclosure provides for a method of growing tumor cell lines or patient-derived xenografts for LGG tumors in an animal (e.g., mouse, rat) including providing a mouse or rat harboring somatic homozygous deletion in the Rag1 or Cxcl10 gene, and implanting an amount of the cells in mice sufficient to grow a tumor.