Automated, high-throughput derivation, characterization and differentiation of induced pluripotent stem cells.

Induced pluripotent stem cells (iPSCs) are an essential tool for modeling how causal genetic variants impact cellular function in disease, as well as an emerging source of tissue for regenerative medicine. The preparation of somatic cells, their reprogramming and the subsequent verification of iPSC pluripotency are laborious, manual processes limiting the scale and reproducibility of this technology. Here we describe a modular, robotic platform for iPSC reprogramming enabling automated, high-throughput conversion of skin biopsies into iPSCs and differentiated cells with minimal manual intervention.

Improved methods for reprogramming human dermal fibroblasts using fluorescence activated cell sorting.

Current methods to derive induced pluripotent stem cell (iPSC) lines from human dermal fibroblasts by viral infection rely on expensive and lengthy protocols. One major factor contributing to the time required to derive lines is the ability of researchers to identify fully reprogrammed unique candidate clones from a mixed cell population containing transformed or partially reprogrammed cells and fibroblasts at an early time point post infection. Failure to select high quality colonies early in the derivation process results in cell lines that require increased maintenance and unreliable experimental outcomes.

RAGE gene deletion inhibits the development and progression of ductal neoplasia and prolongs survival in a murine model of pancreatic cancer.

Background: The receptor for advanced glycation end-products (RAGE) is implicated in pancreatic tumorigenesis. Activating Kras mutations and p16 inactivation are genetic abnormalities most commonly detected as pancreatic ductal epithelium progresses from intraepithelial neoplasia (PanIN) to adenocarcinoma (PDAC).

Objective: The aim of this study was to evaluate the effect of RAGE (or AGER) deletion on the development of PanIN and PDAC in conditional Kras ( G12D ) mice.

RAGE signaling significantly impacts tumorigenesis and hepatic tumor growth in murine models of colorectal carcinoma.

Background: The receptor for advanced glycation end-products (RAGE) is a cell surface receptor implicated in tumor cell proliferation and migration. We hypothesized that RAGE signaling impacts tumorigenesis and metastatic tumor growth in murine models of colorectal carcinoma.

Materials And Methods: Tumorigenesis: Apc (1638N/+) mice were crossed with Rage (-/-) mice in the C57BL/6 background to generate Apc (1638N/+)/Rage (-/-) mice.

Genotype-phenotype analyses of classic neuronal ceroid lipofuscinosis (NCLs): genetic predictions from clinical and pathological findings.

Objective: Genotype-phenotype associations were studied in 517 subjects clinically affected by classical neuronal ceroid lipofuscinosis (NCL).

Methods: Genetic loci CLN1-3 were analyzed in regard to age of onset, initial neurological symptoms, and electron microscope (EM) profiles.

Results: The most common initial symptom leading to a clinical evaluation was developmental delay (30%) in NCL1, seizures (42.

N-terminal segments are the functional domains of CLN3-encoded battenin for protein interactions.

Objective: Batten disease (BD), the juvenile form of neuronal ceroid lipofuscinosis (NCLs), is pathological characterized by finding lysosomal storage of autofluorescent lipofuscins with unique ultrastructural profiles. The gene underlying BD is designated CLN3 and encodes a protein, Battenin, of unknown function that localizes in lysosomes and/or mitochondria. Previously, we hypothesized that Battenin associates with other membrane protein(s) to form a membrane complex.