Transdifferentiation occurs without resetting development-specific DNA methylation, a key determinant of full-function cell identity.

A number of studies have demonstrated that it is possible to directly convert one cell type to another by factor-mediated transdifferentiation, but in the vast majority of cases, the resulting reprogrammed cells are unable to maintain their new cell identity for prolonged culture times and have a phenotype only partially similar to their endogenous counterparts. To better understand this phenomenon, we developed an analytical approach for better characterizing trans-differentiation-associated changes in DNA methylation, a major determinant of long-term cell identity. By examining various models of transdifferentiation both in vitro and in vivo, our studies indicate that despite convincing expression changes, transdifferentiated cells seem unable to alter their original developmentally mandated methylation patterns.

Cedirogant in adults with psoriasis: a phase II, randomized, placebo-controlled clinical trial.

Background: Dysregulated interleukin (IL)-17/IL-23 signalling contributes to psoriasis pathogenesis. Cedirogant is an inverse agonist of nuclear receptor ROR-gamma isoform 2 (RORyt), a key transcription factor responsible for IL-17 synthesis and a regulator of the T helper 17 cell lineage programme.

Objectives: To evaluate the efficacy and safety of cedirogant to treat moderate-to-severe psoriasis.

SULT1A1-dependent sulfonation of alkylators is a lineage-dependent vulnerability of liver cancers.

Adult liver malignancies, including intrahepatic cholangiocarcinoma and hepatocellular carcinoma, are the second leading cause of cancer-related deaths worldwide. Most individuals are treated with either combination chemotherapy or immunotherapy, respectively, without specific biomarkers for selection. Here using high-throughput screens, proteomics and in vitro resistance models, we identify the small molecule YC-1 as selectively active against a defined subset of cell lines derived from both liver cancer types.

Longitudinal Assessment of Bile Duct Loss in Primary Biliary Cholangitis.

Introduction: Bile duct involvement is a key finding of primary biliary cholangitis (PBC). The aim of this study was to evaluate baseline ductopenia and disease progression.

Methods: Retrospective longitudinal histological follow-up of treatment-naive patients with PBC.