Compositions and methods for generating insulin-producing beta cells from pluripotent stem cells are provided. The compositions and methods of the present invention involve stepwise differentiation while the differentiating cells are cultured on a lung tissue-derived acellular scaffold.

The present disclosure provides cell-based compositions for treating diabetes, methods for identifying cells that preferentially differentiate into endoderm cells, and methods for preparing insulin-producing pancreatic cells, as well as related methods of use for treating diseases related to insulin deficiency.

The present disclosure provides cell-based compositions for treating diabetes, methods for identifying cells that preferentially differentiate into endoderm cells, and methods for preparing insulin-producing pancreatic cells, as well as related methods of use for treating diseases related to insulin deficiency.

Disclosed herein are methods, compositions, kits, and agents useful for inducing β cell maturation, and isolated populations of SC-β cells for use in various applications, such as cell therapy.

The present invention relates to methods of generating a population of beta cells from a population of alpha cells, by contacting said population of alpha cells with GABA or a GABA receptor agonist, in combination with a monoclonal glucagon neutralizing antibody or other alpha cell mass regulating compounds, for an improved diabetes therapy.

Provided herein are systems and methods for identifying cell-specific differentiation markers. In particular, provided herein are systems and methods for generating induced pluripotent cells (IPS) from human cells, differentiating the IPS into differentiated cells, and identifying differentiation specific markers.

Disclosed herein are bacterial proteins that increase pancreatic beta (β) cell number and/or proliferation, methods of increasing β cell number and/or proliferation using such proteins, and methods of treating or inhibiting diabetes in a subject by administering such proteins to the subject. In some embodiments, the protein has at least 80% sequence identity to the amino acid sequence set forth as any one of SEQ ID NOs: 1-7, or fragments thereof. Recombinant vectors including a nucleic acid encoding the protein (such as a nucleic acid encoding a protein with at least 80% sequence identity to any one of SEQ ID NOs: 1-7 or fragments thereof) operably linked to a heterologous promoter are also disclosed. Also disclosed are methods of identifying compounds that increase β cell number and/or proliferation by determining the effect of test compounds on β cell number or proliferation in zebrafish pancreas.

The present invention provides a method starting from cells derived from a mammalian endodermal tissue or organ (except for the liver) to produce stein/progenitor cells thereof, which comprises bringing the cells derived from the endodermal tissue or organ into contact in vitro with a TGFβ-receptor inhibitor.

Disclosed herein are methods, compositions, kits, and agents useful for inducing β cell maturation, and isolated populations of SC-β cells for use in various applications, such as cell therapy.

Compositions and methods of producing mammalian cell populations that include a high proportion of pancreatic beta cells are described herein. Such cell populations are useful for treatment of diabetes. Also provided are materials and methods for the direct differentiation of stem cells, such as embryonic stem cells, into functional pancreatic beta cells. The disclosure provides the benefit of direct differentiation, which results in the production of functional pancreatic beta cells efficiently and at low cost.