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Global epigenetic changes during somatic cell reprogramming to iPS cells

Journal of Molecular Cell Biology 2011年第6期3卷 341-350页

作者： Anna Mattout alva biran Eran Meshorer Department of Genetics Institute of Life SciencesThe Hebrew University of JerusalemJerusalem 91904Israel

Embryonic stem cells(ESCs)exhibit unique chromatin features,including a permissive transcriptional program and an open,decondensed chromatin *** pluripotent stem cells(iPSCs),which are very similar to ESCs,hold great promise for therapy and basic ***,the mechanisms by which reprogramming occurs and the chromatin organization that underlies the reprogramming process are largely *** we characterize and compare the epigenetic landscapes of partially and fully reprogrammed iPSCs to mouse embryonic fibroblasts(MEFs)and ESCs,which serves as a standard for *** immuno-fluorescence and biochemical fractionations,we analyzed the levels and distribution of a battery of histone modifications(H3ac,H4ac,H4K5ac,H3K9ac,H3K27ac,H3K4me3,H3K36me2,H3K9me3,H3K27me3,and gH2AX),as well as HP1a and lamin *** find that fully reprogrammed iPSCs are epigenetically identical to ESCs,and that partially reprogrammed iPSCs are closer to ***,combining both time-course reprogramming experiments and data from the partially reprogrammed iPSCs,we find that heterochromatin reorganization precedes Nanog expression and active histone ***,these data delineate the global epigenetic state of iPSCs in conjunction with their pluripotent state,and demonstrate that heterochromatin precedes euchromatin in reorganization during reprogramming.

关键词： chromatin pluripotency reprogramming iPSCs ESCs histone modifications epigenetics

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Elimination of undifferentiated cancer cells by pluripotent stem cell inhibitors

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Journal of Molecular Cell Biology 2014年第3期8卷 267-269页

作者： Uri Ben-David1,2 alva biran2 Paola Scaffidi3,4,5 Christel Herold-Mende6 Markus Boehringer7 Eran Meshorer2 Nissim Benvenisty1,2 Stem Cell Unit Silberman Institute of Life Sciences The Hebrew University Jerusalem 91904 Israel Department of Genetics Silberman Institute of Life Sciences The Hebrew University Jerusalem 91904 Israel National Cancer Institute NIH Bethesda MD 20892 USA UCL Cancer Institute University College London London WC1E 6BT UK Cancer Research UK London Research Institute London WC2A 3LY UK Division of Neurosurgical Research Department of Neurosurgery University of Heidelberg Heidelberg Germany F. Hoffmann-La Roche AG Basel 4070 Switzerland

Dear Editor, According to the cancer stem cell （CSC） hypothesis, cancer ceils are organized in a hierarchical manner （Reya et al, 2001）. Indeed, the differentiation state of cancer cells has been linked to their proliferative potential, drug response, and ability to metastasize （Clevers, 2011）. Targeting self- renewing, undifferentiated cancer ceils could therefore be of importance for the success of cancer therapies. A classical case of a tumor composed of undifferenti- ated and differentiated cells is the tumor induced by pluripotent stem cells （PSCs）（Ben-David and Benvenisty, 2011）. We have recently identified several small mole- cules termed pluripotent-specific inhibitors （PluriSIns） that selectively target undif- ferentiated tumorigenic PSCs （Ben-David et aL, 2013）. Several of these compounds, including PluriSIn#1, inhibit the activity of stearoyl-coA desaturase （SCD1）（Ben- David et al, 2013）. SCD1 is an endoplasmic reticulum （ER）-membrane protein that plays a key role in the biosynthesis of the mono-unsaturated fatty acid oleate. This novel metabolic vulnerability is in line with the unique metabolome described in PSCs （Panopoulos et al, 2012）.

关键词： Pluripotent Stem Cells Hypersensitivity Contact Hypersensitivity cancer cell Circulating Neoplastic Cells

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