A decade of liver organoids: Advances in disease modeling

Liver organoids are three-dimensional cellular tissue models in which cells interact to form unique structures in culture. During the past 10 years, liver organoids with various cellular compositions, structural features, and functional properties have been described. Methods to create these advanced human cell models range from simple tissue culture techniques to complex bioengineering approaches. Liver organoid culture platforms have been used in various research fields, from modeling liver diseases to regenerative therapy. This review discusses how liver organoids are used to model disease, including hereditary liver diseases, primary liver cancer, viral hepatitis, and nonalcoholic fatty liver disease. Specifically, we focus on studies that used either of two widely adopted approaches: differentiation from pluripotent stem cells or epithelial organoids cultured from patient tissues. These approaches have enabled the generation of advanced human liver models and, more importantly, the establishment of patient-tailored models for evaluating disease phenotypes and therapeutic responses at the individual level.

Sialylation is involved in cell fate decision during development, reprogramming and cancer progression

Sialylation, or the covalent addition of sialic acid to the terminal end of glycoproteins, is a biologically important modification that is involved in embryonic development, neurodevelopment, reprogramming, oncogenesis and immune responses. In this review, we have given a comprehensive overview of the current literature on the involvement of sialylation in cell fate decision during development, reprogramming and cancer progression. Sialylation is essential for early embryonic development and the deletion of UDP-GlcNAc 2-epimerase, a rate-limiting enzyme in sialic acid biosynthesis, is embryonically lethal. Furthermore, the sialyltransferase ST6GAL1 is required for somatic cell reprogramming, and its downregulation is associated with decreased reprogramming efficiency. In addition, sialylation levels and patterns are altered during cancer progression, indicating the potential of sialylated molecules as cancer biomarkers. Taken together, the current evidences demonstrate that sialylation is involved in crucial cell fate decision.

PCGF6 regulates stem cell pluripotency as a transcription activator via super-enhancer dependent chromatin interactions

Polycomb group (PcG) ring finger protein 6 (PCGF6), though known as a member of the transcription-repressing complexes, PcG, also has activation function in regulating pluripotency gene expression. However, the mechanism underlying the activation function of PCGF6 is poorly understood. Here, we found that PCGF6 co-localizes to gene activation regions along with pluripotency factors such as OCT4. In addition, PCGF6 was recruited to a subset of the super-enhancer (SE) regions upstream of cell cycle-associated genes by OCT4, and increased their expression. By combining with promoter capture Hi-C data, we found that PCGF6 activates cell cycle genes by regulating SE-promoter interactions via 3D chromatin. Our findings highlight a novel mechanism of PcG protein in regulating pluripotency, and provide a research basis for the therapeutic application of pluripotent stem cells.

Role of McMaster model of family therapy in improving family function of patients with advanced hepatocellular carcinoma / 中国实用护理杂志

Objective We aimed to investigate the role of McMaster model of family therapy in improving family function of patients with advanced hepatocellular carcinoma (HCC).Methods Patients who had advanced HCC and received transarterial embolization (TAE) or transarterial chemoembolization (TACE) from Department of Hepatobiliary Ⅰ,Eastern Hepatobiliary Surgery Hospital between October 1,2012 and June 25,2013 were randomly divided into two groups:the experimental group (51 patients) and the control group (49 patients).The control group received routine family support education.The experimental group not only executed routine family support education,but also was given McMaster model of family therapy according to evaluation results of family assessment device (FAD) on the second and third day of hospitalization.The status of family function of all patients were assessed by FAD on the fnrst day of hospitalization and fourth week after therapy.We compared the status of family function between the two groups.Results In age,gender,educational level,place of residence,occupation,family economic status,medical payment,liver or kidney function,HBV infection,cirrhosis and tumor burden,no statistical differences were found between the experimental group and the control group patients before TAE or TACE.Two groups were dysfunction in communication,roles,affective responsiveness,affective involvement,behavior control,and general function in addition to problem solving before TAE or TACE.No statistical differences were found between two groups.After the therapy,compared with the control group,those patients in the experimental group had a lower level scoring in communication,roles,affective responsiveness,affective involvement,behavior control,and general function in addition to problem solving on the fourth week after the therapy,t value was-2.544,-3.767,-3.904,-2.848,-4.950 and-4.953,the difference had statistical significance.Conclusions McMaster model of family therapy may help to improve family function of patients with advanced HCC.