The Scripps Research Institute

University of California

The J. David Gladstone Institutes, a Testamentary Trust Established Under the Will of J. David Gladstone

The J. David Gladstone Institutes

The J. David Gladstone Institute, a Testamentary Trust Established Under the Will of J. David Gladstone

Saiyong Zhu

Sheng Ding

Yan Shi

Caroline Desponts

Tongxiang Lin

Wenlin Li

Janghwan Kim

Simon Hilcove

Jem A Efe

Hongyan Zhou

Holger Willenbring

Milad Rezvani

Jack Harbell

Ke Li

Matthias Hebrok

Holger Andreas Russ

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.

Methods and compositions for producing pancreatic beta cells

The present invention generally provides methods and compositions for transdifferentiation of an animal cell from a first non-pluripotent cell fate to a second non-pluripotent cell fate. Also provided are methods and compositions for the transdifferentiation of an animal cell from a non-pluripotent mesodermal, endodermal, or ectodermal cell fate to a different non-pluripotent mesodermal, endodermal, or ectodermal cell fate.

Reprogramming of cells to a new fate

The present invention provides for methods, compositions, and kits for producing an induced pluripotent stem cell from a non-pluripotent mammalian cell using a 3'-phosphoinositide-dependent kinase-1 (PDK1) activator or a compound that promotes glycolytic metabolism as well as other small molecules.

Reprogramming cells

Compositions and methods are described herein for inducing reprogramming of non-pluripotent cells across lineage and differentiation boundaries to generate endodermal progenitor cells and hepatocytes. Compositions and methods for expansion of endodermal progenitor cells without loss of phenotype are also described herein.

Generating hepatocytes

The present invention provides for identification and use of small molecules to induce pluripotency in mammalian cells as well as other methods of inducing pluripotency.

Combined chemical and genetic approaches for generation of induced pluripotent stem cells

Compositions and methods of producing mammalian cell populations that include a high proportion of definitive endoderm cells, posterior foregut-like progenitor cells, pancreatic progenitor cells and/or pancreatic beta cells are described herein. Such cell populations are useful for treatment of diabetes.

Generating definitive endoderm and pancreatic progenitor cells

Chemical approaches for generation of induced pluripotent stem cells

Methods and compositions for transdifferentiation of an animal cell from (i) a first pluripotent cell fate to a second nonpluripotent cell fate or (ii) from a non-pluripotent mesodermal, endodermal, or ectodermal cell fate to a different non-pluripotent mesodermal, endodermal, or ectodermal cell fate.

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San Francisco, CA, United States of America

Saiyong Zhu