Provided herein are methods of differentiating stem cells via modulating miR-124, and the differentiated cells thereby. Also provided herein are methods for the treatment of diseases using the differentiated cells.

The present invention provides methods, cell cultures and differentiation media to promote differentiation of pluripotent stem cells to pancreatic endocrine cells expressing PDX1, NKX6.1, and HB9 by culturing in a culture vessel at the air-liquid interface. The invention also provides for in vivo maturation of cells cultured at the air-liquid interface.

The present invention provides improved methods and compositions based on microvesicles for the treatment of various diseases, disorders and conditions. In particular, the present invention encompasses the recognition that microvesicles contain specific microRNAs which may function as intercellular regulators involved in cell or tissue regeneration, remodeling, reconstruction, reprogramming or transdifferentiation. Thus, among other things, the present invention provides methods and compositions based on microvesicles and/or associated microRNAs that provide more predictable and effective therapeutic results.

Biomarkers relating to pancreatic Beta-cell function, pancreatic Beta-cell glucose sensitivity, insulin resistance, and/or pancreatic Beta-cell-related disorders are provided. Methods based on the same biomarkers are also provided.

Provided herein are methods of differentiating stem cells via modulating miR-124, and the differentiated cells thereby. Also provided herein are methods for the treatment of diseases using the differentiated cells.

The invention provides stem cell derived beta-pancreatic cells and animal models of T2D in which cells have been grafted. The stem cells bear a mutated form of SLC30A8 conferring protection or susceptibility to T2D. The cells and animal models can be used for drug screening as well as to provide insights into the mechanism of T2D and potentially new therapeutic and diagnostic targets.

ZSCAN4, a gene expressed in ES cells and 2-cell stage embryos, has been previously shown to regulate telomere elongation and genome stability in mouse ES cells. It is disclosed herein that in the adult human pancreas, a small number of ZSCAN4-positive cells are present among cells located in the islets of Langerhans, acini, and ducts. These data disclosed herein indicates that expression of ZSCAN4 is a marker for rare stem/progenitor cells in adult human pancreas. Thus, provided herein is a method of isolating pancreatic stem cells or progenitor cell from a sample by detecting expression of ZSCAN4. Also provided is a method of treating diabetes by isolating ZSCAN4.sup.+ pancreatic stem cells or progenitor cells, expanding the cells in vitro and transplanted the expanded cells into the subject. The expanded ZSCAN4.sup.+ cells can optionally be differentiated into pancreatic cells before transplanting the cells into the subject. Further provided is an in vivo method of expanding a population of pancreatic stem cells or progenitor cells in a subject by delivering a ZSCAN4 protein, a ZSCAN4 nucleic acid sequence, or an agent that increases expression of ZSCAN4 to the pancreas of the subject.

Disclosed herein are methods for generating augmented SC- cells, and isolated populations of augmented SC- cells for use in various applications, such as cell therapy.

Disclosed herein are methods for generating SC- cells, and isolated populations of SC- cells for use in various applications, such as cell therapy.

Methods, kits, compositions, and systems are provided for culturing pluripotent stem cells to produce populations of cells comprising beta-like cells (e.g., pancreatic lineage, glucose-responsive, and/or insulin-producing). In particular, culture conditions are provided that result in the generation of beta-like cells from a starting culture of human pluripotent stem cells.