The presently disclosed subject matter provides for in vitro methods of inducing differentiation of stem cells (e.g., human stem cells) into proprioceptors, proprioceptors generated by such methods, and compositions comprising such proprioceptors. The presently disclosed subject matter also provides for uses of such proprioceptors for preventing and/or treating disorders of proprioceptor neurons and/or neurodegenerative disorders (e.g., Friedreich's Ataxia).

Disclosed herein are methods for directing a differentiation protocol to produce cells of a desired cell fate, such as SC-β and/or SC-α cells.

Disclosed is a spheroid liver organoid comprising hepatic lineage cells such as human hepatocytes, hepatic stellate cells, and liver sinusoidal endothelial cells. Also provided are methods of using spheroid liver organoids for applications related to drug screening and toxicity screening. In particular, spheroid liver organoids are useful for high-throughput screens to identify compounds having efficacy for treating liver disease.

In certain example embodiments, the invention provides a method of generating an ex vivo cell-based system comprising dissociating an original tissue sample obtained from a subject into a single cell population; determining an in vivo phenotype of the tissue sample by conducting single-cell RNA analysis on a first portion of the single cells; establishing an ex vivo cell-based system from a second portion of the single cells; and culturing the ex vivo cell-based system in a medium or conditions selected to maintain the in vivo phenotype. In some embodiments, the original tissue sample is a tumor tissue sample, such as a pancreatic ductal adenocarcinoma (PDAC) tumor sample.

A method for arterial endothelial-enhanced functional T cell generation is provided. In the method, arterial endothelial cells enhance functional T cell generation by promoting the generation of hematopoietic progenitor cells with T-lineage bias. The first stage of T cell differentiation from human pluripotent stem cells (hPSCs) is optimized, and it is found that hPSC-derived autologous arterial endothelial cells increase the T cell potential of hematopoietic progenitor cells. Moreover, the T cells generated by arterial endothelial cell priming share similar function to that of human peripheral blood T cells. hPSC-derived CD19-CAR-T cells have been verified to have tumor-killing effects both in vivo and in vitro. The established hPSC-T differentiation system would provide a valuable resource for chimeric antigen receptor T cell (CAR-T) therapy.

An amplifying method of pancreatic cells is provided. The amplifying method includes performing digestion, resuspension, discontinuous density gradient centrifugation treatment and amplifying treatment sequentially. The mammalian pancreatic duct is used as the source of pancreatic precursor-like cells in the amplifying method, and islet cells and acinar cells in the cell clusters obtained by the discontinuous density gradient centrifugation treatment are removed. It is beneficial to improve the yield of the pancreatic precursor-like cells availably, and avoid the ethical restrictions and possible carcinogenic risks caused by using the embryonic stem cells. The amplifying medium used comprises a reprogramming substance composed of several small molecule compounds. It can avoid the risks of non-specific and off-target deletion that are easily caused by the use of the gene-editing methods to change the gene sequence. Also provided is a differentiation method and an application of the pancreatic precursor-like cells obtained by the amplifying method.

Provided is a method for isolating a ureteric bud tip cell from cells, a tissue, or an organoid comprising the ureteric bud tip cell, comprising the following steps of contacting the cells, tissue, or organoid comprising the ureteric bud tip cell with a very low density lipoprotein receptor (VLDL-R) binding agent, and isolating the ureteric bud tip cell using the binding agent as an indicator.

According to a production method for a brain organoid, comprising a step 1 of carrying out suspension culture of human pluripotent stem cells having a mutation in at least one or more base sequences in an exon selected from the group consisting of an exon 9, an exon 10, an exon 11, an exon 12, and an exon 13 of a microtubule-associated protein tau (MAPT) gene, and having a mutation in at least one or more base sequences in an intron 10 of the MAPT gene, it is possible to produce a brain organoid having a phosphorylated 3-repeat tau protein and a phosphorylated 4-repeat tau protein.

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 a limb bud mesenchymal cell population, which is derived from mammalian lateral plate mesoderm cells, and is PRRX1 protein-positive.