The Cleveland Clinic Foundation

University of Colorado

Janssen Biotech, Inc.

Jan Jensen

Howard R Davidson

John C Hutton

Michael A Bukys

Jean Xu

Xiaoling Qu

Janet M Wenzlau

Oliver Wessely

Uyen Wessely

Provided herein are compositions, systems, kits, and methods for generating dorsal foregut endoderm (DFE) cells by contacting pluripotent stem cells with a retinoic acid signaling pathway agonist and a bone morphogenetic (BMP) pathway inhibitor without exposing the stem cells to a transforming growth factor beta (TGFβ) pathway agonist. In certain embodiments, the DFE cells are contacted with a retinoic acid signaling pathway agonist and a FGFR pathway inhibitor to generate pancreatic endoderm (PE) cells (e.g., with dorsal identity). In other embodiments, the PE cells are contacted with an ALK5 inhibitor and a Notch inhibitor to generate endocrine cells (e.g., insulin expressing endocrine cells). In certain embodiments, compositions, systems, kits, and methods are provided for generating anterior domain endoderm (ADE) cells.

Generating dorsal foregut, and anterior domain, endoderm cells

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.

Generating human podocyte cells

The invention is based, in part, on the discovery that a polypeptide, referred to herein as Betacam, is selectively expressed on the surface of pancreatic islet cells. Thus, in one aspect, the invention is directed to compositions comprising Betacam or that can be used to detect Betacam. In another aspect, the invention provides methods of detecting (e.g., non-invasively) pancreatic beta cells from a mammalian cell source. Another aspect of the invention is directed to cellular purification of pancreatic beta cells from a heterogeneous cell source of multiple kinds. In another aspect, the invention provides methods of identifying agents that modulate activity of Betacam. In yet another aspect, the invention provides for improved treatment and diagnosis of diabetes.

Method for detecting and purifying pancreatic beta cells

Described is the identification of ZnT8 as an autoantigen target in type I autoimmune diabetes (T1D), other autoimmune disease, and other diabetes-linked diseases and conditions. Also described are a variety of therapeutic, diagnostic, and prognostic tools and methods based on this discovery. The identification of genetic variation in ZnT8 as an important player in the initiation of the disease process and the progression of autoimmunity to clinical diabetes is disclosed.

Diagnostic and therapeutic target for autoimmune diseases and uses thereof

The present invention provides methods to promote the differentiation of pluripotent stem cells into cells expressing markers characteristic of the pancreatic endocrine lineage that co-express PDX1, NKX6.1, but do not express CDX2 and NGN3.

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Shaker Heights, OH, United States of America

Jan Jensen