Goding C.R.,University of Oxford |
Pei D.,CAS Guangzhou Institute of Biomedicine and Health |
Lu X.,University of Oxford
Nature Reviews Cancer
The ability of stem cells to self-renew and generate different lineages during development and organogenesis is a fundamental, tightly controlled, and generally unidirectional process, whereas the 'immortality' of cancer cells could be regarded as pathological self-renewal. The molecular mechanisms that underpin the generation of induced pluripotent stem cells are remarkably similar to those that are deregulated in cancer-so much so that aberrant reprogramming is tumorigenic. The similarities also suggest that mutations in genes implicated in DNA methylation dynamics might represent a hallmark of cancers with a stem cell origin, and they highlight an alternative view of cancer that may be of clinical benefit. © 2014 Macmillan Publishers Limited. Source
Liu N.,CAS Guangzhou Institute of Biomedicine and Health
The International journal of developmental biology
Zfyve9 is a FYVE domain protein first identified as a binding partner for SMAD2/3. In vitro studies indicate that it can function either positively or negatively in the TGF-beta signaling pathway depending on the cell lines used. However, the in vivo function of this protein remains to be investigated. We first analyzed the tissue distribution of zebrafish zfyve9a by in situ hybridization. To investigate the in vivo function of this gene, we performed morpholino mediated loss-of-function assays. We analyzed the expression patterns of liver (cp and fabp10a), pancreas (trypsin and insulin) or gut (fabp2) specific markers to determine whether the formation of these organs is affected by zfyve9a knockdown. We determined the specification of hepatoblast in the zfyve9a morphants (prox1a) and investigated the proliferation and survival of hepatic cells in the morphants by P-H3 staining and TUNEL assay respectively. We report here that zfyve9a is enriched in the zebrafish embryonic liver and required for hepatogenesis. Morpholino mediated knockdown of zfyve9a inhibits the formation of liver by day 4 while the other endoderm-derived organs appear unaffected. We demonstrated that the specification of hepatoblasts is normal in the zfyve9a morphants; however, the proliferation rate of these cells is reduced. Thus, our results reveal the liver-specific function of zfyve9a during early embryogenesis and indicate that the zfyve9a mediated signal is essential for the proliferation of hepatic cells during the expansion of liver bud. Source
CAS Guangzhou Institute of Biomedicine, Health and University of Vienna | Date: 2011-12-23
Methods for generating iPSCs and differentiated cells of interest by reprogramming donor cells that have been obtained in a non-invasive manner. In particular, the donor cells are exfoliated epithelial urine cells. The differentiated cells can be obtained by differentiation of the reprogrammed iPSCs or by direct reprogramming the urine cells.
CAS Guangzhou Institute of Biomedicine and Health | Date: 2014-07-02
The compounds according to formula (VIII), their pharmaceutically acceptable acid or base addition salts, and the uses thereof. These compounds and their pharmaceutically acceptable acid or base addition salts can be used for preparing medicaments for modulating estrogen related receptors (ERR), and treating metabolic diseases, such as high blood fat, fatty liver, hyperglycemia, diabetes, obesity. The substituents of the formula are defined in the description.
Wang W.,CAS Guangzhou Institute of Biomedicine and Health |
Wong C.-W.,CAS Guangzhou Institute of Biomedicine and Health
Journal of Molecular Medicine
Peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) serves as an inducible coactivator for a number of transcription factors to control energy metabolism. Insulin signaling through Akt kinase has been demonstrated to phosphorylate PGC-1α at serine 571 and downregulate its activity in the liver. Statins are 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors that reduce cholesterol synthesis in the liver. In this study, we found that statins reduced the active form of Akt and enhanced PGC-1α activity. Specifically, statins failed to activate an S571A mutant of PGC-1α. The activation of PGC-1α by statins selectively enhanced the expression of energy metabolizing enzymes and regulators including peroxisome proliferator-activated receptor α, acyl-CoA oxidase, carnitine palmitoyl transferase-1A, and pyruvate dehydrogenase kinase 4. Importantly, a constitutively active form of Akt partially reduced the statin-enhanced gene expression. Our study thus provides a plausible mechanistic explanation for the hypolipidemic effect of statin through elevating the rate of β-oxidation and mitochondrial Kreb's cycle capacity to enhance fatty acid utilization while reducing the rate of glycolysis. © 2009 Springer-Verlag. Source