Project description:Understanding gene expression profile and transcriptional regulation of healthy adult human hepatocytes Gene expression was analyzed
Project description:Generation of human fibroblast-derived hepatocytes capable of extensive proliferation, as evidenced by significant liver repopulation of mice. Unlike current protocols for deriving hepatocytes from human fibroblasts, ours did not generate iPSCs, but shortcut reprogramming to pluripotency to generate an induced multipotent progenitor cell (iMPC) stage from which endoderm progenitor cells (iMPC-EPCs) and subsequently hepatocytes (iMPC-Heps) could be efficiently differentiated. After transplantation into an immune-deficient mouse model of human liver failure, iMPC-Heps were able to engraft and proliferate, and acquired levels of hepatocyte function similar to adult hepatocytes. Microarray analysis has been used to show: 1. post-transplant maturation in vivo of iMPC-Heps compared to aHeps, 2. differences between iMPC-Heps and freshly isolated aHeps in vitro, 3. similar profile of freshly isolated aHeps to aHeps and iMPC-Heps in vivo, and 4. similarities of expression levels of most, but not all, genes between iMPC-Heps and iPSC-Heps in vitro.
Project description:Generation of human fibroblast-derived hepatocytes capable of extensive proliferation, as evidenced by significant liver repopulation of mice. Unlike current protocols for deriving hepatocytes from human fibroblasts, ours did not generate iPSCs, but shortcut reprogramming to pluripotency to generate an induced multipotent progenitor cell (iMPC) stage from which endoderm progenitor cells (iMPC-EPCs) and subsequently hepatocytes (iMPC-Heps) could be efficiently differentiated. After transplantation into an immune-deficient mouse model of human liver failure, iMPC-Heps were able to engraft and proliferate, and acquired levels of hepatocyte function similar to adult hepatocytes. Microarray analysis has been used to show: 1. post-transplant maturation in vivo of iMPC-Heps compared to aHeps, 2. differences between iMPC-Heps and freshly isolated aHeps in vitro, 3. similar profile of freshly isolated aHeps to aHeps and iMPC-Heps in vivo, and 4. similarities of expression levels of most, but not all, genes between iMPC-Heps and iPSC-Heps in vitro. We isolated repopulating nodules of iMPC-Heps and aHeps by laser-capture microscopy (LCM) around 9 months after transplantation and analyzed their gene expression on the microarray, together with RNA from in vitro samples.
Project description:Genome-wide expression profiling has been performed in malignant HepG2 cells and compared to the expression in normal human hepatocytes. 56 ucRNAs, representing 11% of all ucRNAs analyzed, were aberrantly and significantly (p<0.05) expressed in malignant HepG2 cells compared to non-malignant human hepatocytes.
Project description:To analyze stem/progenitor cell function, we purified hepatocytes derived from adult livers and fetal hepatoblasts derived from embryonic day 13 livers. Compared gene expression in E13 hepatoblasts and adult hepatocytes derived from C57BL/6NCr mice
Project description:Comparison of gene expression in adult male mouse livers between wildtype mice and Transgenic mice expressing human Small Heterodimer Partner in hepatocytes.
Project description:To analyze stem/progenitor cell function, we purified hepatocytes derived from adult livers and fetal hepatoblasts derived from embryonic day 13 livers.