Abstract: Disclosed herein are homology-independent targeted integration methods of integrating an exogenous DNA sequence into a genome of a non-dividing cell and compositions for such methods. Methods herein comprise contacting the non-dividing cell with a composition comprising a targeting construct comprising the exogenous DNA sequence and a targeting sequence, a complementary strand oligonucleotide homologous to the targeting sequence, and a nuclease, thereby altering the genome of the non-dividing cell.

Abstract: Disclosed herein are homology-independent targeted integration methods of integrating an exogenous DNA sequence into a genome of a non-dividing cell and compositions for such methods. Methods herein comprise contacting the non-dividing cell with a composition comprising a targeting construct comprising the exogenous DNA sequence and a targeting sequence, a complementary strand oligonucleotide homologous to the targeting sequence, and a nuclease, thereby altering the genome of the non-dividing cell.

Abstract: Compositions and methods modulating the steady state of cells are provided. The compositions include metabolites (C1 metabolites and C1 metabolite cocktails (C1-MIM) for use in inducing cells into a different state from their steady state, for example, into a less differentiated state, when compared to their original state before treatment. The C1 metabolites include methionine, SAM (S-adenosyl methionine), threonine, glycine, putrescine, and cysteine. The metabolites are used to supplement cell culture media, and accordingly, cells culture media supplemented with the disclosed metabolites (MIM supplemented media) are also provided. The method includes: contacting a cell with the C1 metabolites for a sufficient period of time to result in reprograming the cell into a different state from their steady, for example, into a less differentiated state having progenitor-like characteristics (MIM-Cells).

Abstract: Disclosed herein are homology-independent targeted integration methods of integrating an exogenous DNA sequence into a genome of a non-dividing cell and compositions for such methods. Methods herein comprise contacting the non-dividing cell with a composition comprising a targeting construct comprising the exogenous DNA sequence and a targeting sequence, a complementary strand oligonucleotide homologous to the targeting sequence, and a nuclease, thereby altering the genome of the non-dividing cell.

Abstract: Provided herein are blastoids and methods for producing the same that are obtained from an extended pluripotent stem (EPS) cell. The herein-disclosed methods provide a unique and highly malleable in vitro system for studying early preimplantation development. Also provided are EPS-blastoids derived from a somatic cell.

Abstract: Methods are provided for treating osteoarthritis by administering ?Klotho protein and sTGF?-R2 protein to a site within a mammal exhibiting symptoms of osteoarthritis, such as a knee joint. The ?Klotho protein and the sTGF?-R2 protein are both present at the osteoarthritic site.

Abstract: Provided herein are methods and compositions for editing a target genome in a cell comprising contacting the cell with (i) a single homology arm construct comprising a replacement sequence and a targeted endonuclease cleavage site; and (ii) a targeted endonuclease, wherein the replacement sequence comprises at least one nucleotide difference compared to the target genome and wherein the target genome comprises a sequence homologous to the targeted endonuclease cleavage site.

Abstract: Provided are modified guide RNAs (gRNAs), including dead guide RNAs (dgRNAs) with increased GC content and/or decreased repetitive content, as well as compositions and kits including such dgRNAs, which can be used in a targeted gene activation system, for example to increase expression of a gene to treat a disease in vivo. Such methods increase targeted gene expression, without creating DNA double strand breaks (DSBs).

Abstract: This disclosure provides ungulate embryonic stem cells (ESCs) derived from the inner cell mass of pre-implantation blastocysts or pluripotent cells from embryos. From an agricultural and biomedical perspectives, the derivation of stable ESCs from domestic ungulates is important for genomic testing and selection, genetic engineering, and providing an experimental tool for studying human diseases. Cattle are one of the most important domestic ungulates that are commonly used for food and bioreactors.

Abstract: Disclosed herein are homology-independent targeted integration methods of integrating an exogenous DNA sequence into a genome of a non-dividing cell and compositions for such methods. Methods herein comprise contacting the non-dividing cell with a composition comprising a targeting construct comprising the exogenous DNA sequence and a targeting sequence, a complementary strand oligonucleotide homologous to the targeting sequence, and a nuclease, thereby altering the genome of the non-dividing cell.

Abstract: Disclosed herein are chimeric mammals, such as a chimeric mammal comprising cells derived from at least a first mammal and a second mammal, wherein the cells from the first mammal comprise a genetic modification at one or more loci and the cells from the second mammal form at least one organ or tissue, wherein the first and second mammals are different species.

Abstract: Provided herein are self-renewable nephron progenitor cell (srNPC) and methods for making and using.

Abstract: Methods of preventing the transmission of a mitochondrial disease, disorder, or condition using mitochondria-targeted enzymes or mRNA encoding mitochondria-targeted enzymes. The methods as described herein can specifically eliminate mitochondrial DNA (mtDNA) mutations in the germline.

Abstract: Methods for heart regeneration are provided. The invention provided herein includes methods of modulating proliferation of cardiomyocytes using small molecules and micro RNAs. In embodiments, the methods provided may be used to increase proliferation or cardiomyocytes. Further provided are methods to be used for the treatment of myocardial infarction.

Abstract: Methods for heart regeneration are provided. The invention provided herein includes methods of modulating proliferation of cardiomyocytes using small molecules and micro RNAs. In embodiments, the methods provided may be used to increase proliferation or cardiomyocytes. Further provided are methods to be used for the treatment of myocardial infarction.

Abstract: Methods for heart regeneration are provided. The invention provided herein includes methods of modulating proliferation of cardiomyocytes using small molecules and micro RNAs. In embodiments, the methods provided may be used to increase proliferation or cardiomyocytes. Further provided are methods to be used for the treatment of myocardial infarction.

Abstract: Provided herein are, inter alia, methods of generating vascular progenitor cells from primary cells without reprogramming the primary cell into a pluripotent stem cell. The vascular progenitors provided herein may be used to form endothelial cells or smooth muscle cells. Further provided are isolated mutlitpotent cells useful to form vascular progenitor cells.

Abstract: Provided herein are methods and compositions for generating vascular progenitor cells that can in turn be differentiated into endothelial, smooth muscle, and hematopoietic cells. The present methods provide a faster, safer, and more efficient in vitro differentiation program than existing methodologies. The differentiated cells can be used for research and therapeutic applications, such as cell transplantation.

Abstract: There are provided, inter alia, methods for forming (e.g. transgeneration of) hematopoietic stem cells from mesenchymal stem cells.

Abstract: Methods and compositions for generating adipose-derived induced pluripotent stem cells for humans and animals and their use are provided.