Abstract: Methods and compositions are provided for generating F0 fertile XY female animals. The methods and compositions involve making XY pluripotent or totipotent animal cells, in vitro cell cultures, or embryos that are capable of producing a fertile female XY animal in an F0 generation. Such cells, embryos, and animals can be made by silencing a region of the Y chromosome. Optionally, the cells can also be cultured in feminizing medium such as a low-osmolality medium and/or can be modified to decrease the level and/or activity of an Sry protein. Methods and compositions are also provided for silencing a region of the Y chromosome in an XY pluripotent or totipotent animal cell, or in vitro cell cultures, embryos, or animals derived therefrom, by maintaining an XY pluripotent or totipotent animal cell in a feminizing medium.

Abstract: The invention discloses using secreted splicing variant of mammal Klotho (s-KL) as an agent for the prevention and/or treatment of cognitive and/or behaviour impairments. It also refers to gene constructs and expression vectors useful in gene therapy for the delivery of said s-KL variant to the central nervous system of a mammal, in particular a rodent or a human. Pharmaceutical compositions comprising either the protein s-KL or any gene construct for expressing the protein in the CNS are also disclosed.

Abstract: Provided herein are nutrient media formulations and engineered growth factors, and methods thereof, useful for the production of slaughter-free meat.

Abstract: Disclosed herein are universal donor stem cells and related methods of their use and production. The universal donor stem cells disclosed herein are useful for overcoming the immune rejection in cell-based transplantation therapies. In certain embodiments, the universal donor stem cells disclosed herein do not express one or more MHC-I and MHC-II human leukocyte antigens. Similarly, in certain embodiments, the universal donor stem cells disclosed herein do not express one or more human leukocyte antigens (e.g., HLA-A, HLA-B and/or HLA-C) corresponding to MHC-I and MHC-II human leukocyte antigens, thereby rendering such cells hypoimmunogenic.

Abstract: Disclosed herein are universal donor stem cells and related methods of their use and production. The universal donor stem cells disclosed herein are useful for overcoming the immune rejection in cell-based transplantation therapies. In certain embodiments, the universal donor stem cells disclosed herein do not express one or more MHC-I and MHC-II human leukocyte antigens. Similarly, in certain embodiments, the universal donor stem cells disclosed herein do not express one or more human leukocyte antigens (e.g., HLA-A, HLA-B and/or HLA-C) corresponding to MHC-I and MHC-II human leukocyte antigens, thereby rendering such cells hypoimmunogenic.

Abstract: Provided herein are compositions, systems, kits, and methods for generating human podocyte cells by contacting human nephron progenitor cells with an FGFR pathway inhibitor, a BMP pathway inhibitor, and a WNT pathway inhibitor. In certain embodiments, the nephron progenitor cells are further contacted with at least one factor selected from: BMP4, BMP7, lysophosphatidic acid, and gamma-secretase inhibitor XX. In certain embodiments, the contacting the nephron progenitor cells is performed under serum-free conditions.

Abstract: The disclosure provides a method of freezing an aggregate of pluripotent stem cell-derived cardiomyocytes, comprising: (i) immersing an aggregate of pluripotent stem cell-derived cardiomyocytes in a cryoprotective solution; and (ii) freezing the aggregate immersed in the cryoprotective solution. The disclosure also provides a frozen aggregate of pluripotent stem cell-derived cardiomyocytes frozen by the method.

Abstract: An animal model (e.g., mouse) and method of use, and cell culture assay method, for characterizing or screening a test compound for its effect on late onset Alzheimer's disease (LOAD). The test compound may be used as a therapeutic agent for treatment of Alzheimer's disease (AD). The AD animal model may be haploinsufficient for Shugoshin 1 (Sgo1) gene, or may comprise a genetic modification enabling modulation of Sgo1 expression in the brain of the animal when exposed to an Sgo1 expression-modulating compound, such as tamoxifen. After the test compound is administered to the animal model, the presence or amount of an AD biomarker is assessed or measured.

Abstract: This disclosure relates to genetically modified animals and cells with humanized light chain immunoglobulin locus and/or humanized heavy chain immunoglobulin locus. In one aspect, the endogenous light chain immunoglobulin locus comprises a limit number of human IGKV genes and human IGKJ genes.

Abstract: Methods and compositions for modifying the coding sequence of endogenous genes using rare-cutting endonucleases and transposases. The methods and compositions described herein can be used to modify the coding sequence of endogenous genes.

Abstract: An object of the present invention is induction of CD4-positive T cells from pluripotent stem cells. This object is achieved by production of CD4-positive T cells by introducing a CD4 gene or a gene product thereof into T cells induced from pluripotent stem cells.

Abstract: Human pluripotent stem cells (hPSCs) are promising cell source to produce therapeutic endocrine cells for diabetes treatment. A gel solution made by decellularized tissue-specific extracellular matrix (dpECM) significantly promotes three-dimensional (3D) islet-like organogenesis during induced hPSC differentiation into endocrine lineages. Islet organoids are self-organized even in a two-dimensional (2D) culture mode. Cells derived from hPSCs differentiated on such ECM coated substrates exhibit similar cellular composition to native pancreatic islets. These cells express islet signature markers insulin, PDX-1, C-peptide, MafA, glucagon, somatostatin, and pancreatic polypeptide, and secrete more insulin in response to glucose level compared to a traditional matrix substrate (Matrigel). The dpECM facilitates generating more C-peptide+/glucagon? cells rather than C-peptide+/glucagon+ cells. Remarkably, dpECM also facilitated intra-organoid vascularity by generating endothelial cells and pericytes.

Abstract: The present invention relates to a chimeric antigen receptor (CAR) which comprises an antigen-binding domain which selectively binds TCR beta constant region 1 (TRBC1) or TRBC2; cells; such a T cells comprising such a CAR; and the use of such cells for the treatment of a T-cell lymphoma or leukaemia in a subject.

Abstract: The present invention relates to a chimeric antigen receptor (CAR) which comprises an antigen-binding domain which selectively binds TCR beta constant region 1 (TRBC1) or TRBC2; cells; such a T cells comprising such a CAR; and the use of such cells for the treatment of a T-cell lymphoma or leukaemia in a subject.

Abstract: The present invention provides methods, cell cultures and differentiation media to promote differentiation of pluripotent stem cells to pancreatic endocrine cells of a mature phenotype. The resulting pancreatic endocrine cells express single hormonal insulin, PDX1, NKX6.1, and MAFA. In one or more differentiation stages, culturing may be carried out in a culture vessel at the air-liquid interface.

Abstract: The present invention relates to methods of developing genetically engineered, preferably non-alloreactive T-cells for immunotherapy. This method involves the use of RNA-guided endonucleases, in particular Cas9/CRISPR system, to specifically target a selection of key genes in T-cells. The engineered T-cells are also intended to express chimeric antigen receptors (CAR) to redirect their immune activity towards malignant or infected cells. The invention opens the way to standard and affordable adoptive immunotherapy strategies using T-Cells for treating cancer and viral infections.

Abstract: The invention provides for methods of differentiating pancreatic endocrine cells into pancreatic beta cells expressing PDX1, NKX6.1, MAFA, UCN3 and SLC2A. These pancreatic beta cells may be obtained by step-wise differentiation of pluripotent stem cells. The pancreatic beta cells exhibit glucose-dependent mitochondrial respiration and glucose-stimulated insulin secretion similar to islet cells.

Abstract: The invention relates to a long DH (LDH) cassette comprising a recombinant DH construct comprising at least two DH gene segments encoding at least 10 amino acids of the HCDR3 amino acid sequence, wherein at least one of the DH gene segments is a heterologous DH gene segment; an immunoglobulin heavy chain locus and a transgenic non-human animal comprising the same; and their use in producing an immunoglobulin library with long HCDR3 regions.

Abstract: Production of beta-cells from stem cells from pluripotent stem cells have always been significantly lacking in at least one of the following properties: 1) functional properties related to insulin-production and glucose signaling response, 2) mature phenotype such as biochemical markers or cell structures, 3) efficiency in production of differentiated cells. Described herein is multistep differentiation protocol which substantially overcomes all of the existing limitations. Pluripotent stem cells, including induced pluripotent stem cells (iPSCs), and embryonic stem cells (ESCs) can be differentiated using an embryoid body (EB) formation step, followed by B maturation via endothelial cells (EC) co-culturing and incubation with a sequential series of bone morphogenic protein (BMP)-related growth factor cocktails. The resulting cells displayed functional properties, including insulin-production and glucose signaling response, and mature phenotype of C-peptide expression.

Abstract: A culture medium is disclosed which comprises STAT3 activator, an ERK1/2 inhibitor and an Axin stabilizer, and optionally also a PKC inhibitor. Cell cultures comprising same and uses thereof are also disclosed.