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  • 1
    Publication Date: 2013-09-21
    Description: Somatic cells can be inefficiently and stochastically reprogrammed into induced pluripotent stem (iPS) cells by exogenous expression of Oct4 (also called Pou5f1), Sox2, Klf4 and Myc (hereafter referred to as OSKM). The nature of the predominant rate-limiting barrier(s) preventing the majority of cells to successfully and synchronously reprogram remains to be defined. Here we show that depleting Mbd3, a core member of the Mbd3/NuRD (nucleosome remodelling and deacetylation) repressor complex, together with OSKM transduction and reprogramming in naive pluripotency promoting conditions, result in deterministic and synchronized iPS cell reprogramming (near 100% efficiency within seven days from mouse and human cells). Our findings uncover a dichotomous molecular function for the reprogramming factors, serving to reactivate endogenous pluripotency networks while simultaneously directly recruiting the Mbd3/NuRD repressor complex that potently restrains the reactivation of OSKM downstream target genes. Subsequently, the latter interactions, which are largely depleted during early pre-implantation development in vivo, lead to a stochastic and protracted reprogramming trajectory towards pluripotency in vitro. The deterministic reprogramming approach devised here offers a novel platform for the dissection of molecular dynamics leading to establishing pluripotency at unprecedented flexibility and resolution.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rais, Yoach -- Zviran, Asaf -- Geula, Shay -- Gafni, Ohad -- Chomsky, Elad -- Viukov, Sergey -- Mansour, Abed AlFatah -- Caspi, Inbal -- Krupalnik, Vladislav -- Zerbib, Mirie -- Maza, Itay -- Mor, Nofar -- Baran, Dror -- Weinberger, Leehee -- Jaitin, Diego A -- Lara-Astiaso, David -- Blecher-Gonen, Ronnie -- Shipony, Zohar -- Mukamel, Zohar -- Hagai, Tzachi -- Gilad, Shlomit -- Amann-Zalcenstein, Daniela -- Tanay, Amos -- Amit, Ido -- Novershtern, Noa -- Hanna, Jacob H -- England -- Nature. 2013 Oct 3;502(7469):65-70. doi: 10.1038/nature12587. Epub 2013 Sep 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24048479" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; Cells, Cultured ; Cellular Reprogramming/genetics/*physiology ; DNA-Binding Proteins/genetics ; Embryonic Stem Cells ; Female ; Gene Expression Regulation ; HEK293 Cells ; Humans ; Induced Pluripotent Stem Cells/*physiology ; Male ; Mice ; *Models, Biological ; Transcription Factors/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2015-04-02
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rais, Yoach -- Zviran, Asaf -- Geula, Shay -- Gafni, Ohad -- Chomsky, Elad -- Viukov, Sergey -- Mansour, Abed AlFatah -- Caspi, Inbal -- Krupalnik, Vladislav -- Zerbib, Mirie -- Maza, Itay -- Mor, Nofar -- Baran, Dror -- Weinberger, Leehee -- Jaitin, Diego A -- Lara-Astiaso, David -- Blecher-Gonen, Ronnie -- Shipony, Zohar -- Mukamel, Zohar -- Hagai, Tzachi -- Gilad, Shlomit -- Amann-Zalcenstein, Daniela -- Tanay, Amos -- Amit, Ido -- Novershtern, Noa -- Hanna, Jacob H -- England -- Nature. 2015 Apr 30;520(7549):710. doi: 10.1038/nature14369. Epub 2015 Apr 1.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25830885" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2014-08-12
    Description: Chromatin modifications are crucial for development, yet little is known about their dynamics during differentiation. Hematopoiesis provides a well-defined model to study chromatin state dynamics; however, technical limitations impede profiling of homogeneous differentiation intermediates. We developed a high-sensitivity indexing-first chromatin immunoprecipitation approach to profile the dynamics of four chromatin modifications across 16 stages of hematopoietic differentiation. We identify 48,415 enhancer regions and characterize their dynamics. We find that lineage commitment involves de novo establishment of 17,035 lineage-specific enhancers. These enhancer repertoire expansions foreshadow transcriptional programs in differentiated cells. Combining our enhancer catalog with gene expression profiles, we elucidate the transcription factor network controlling chromatin dynamics and lineage specification in hematopoiesis. Together, our results provide a comprehensive model of chromatin dynamics during development.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4412442/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4412442/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lara-Astiaso, David -- Weiner, Assaf -- Lorenzo-Vivas, Erika -- Zaretsky, Irina -- Jaitin, Diego Adhemar -- David, Eyal -- Keren-Shaul, Hadas -- Mildner, Alexander -- Winter, Deborah -- Jung, Steffen -- Friedman, Nir -- Amit, Ido -- 1P50HG006193/HG/NHGRI NIH HHS/ -- P50 HG006193/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2014 Aug 22;345(6199):943-9. doi: 10.1126/science.1256271. Epub 2014 Aug 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology, Weizmann Institute of Science, Rehovot, Israel. ; Institute of Life Sciences, The Hebrew University, Jerusalem, Israel. School of Computer Science and Engineering, The Hebrew University, Jerusalem, Israel. ; Institute of Life Sciences, The Hebrew University, Jerusalem, Israel. School of Computer Science and Engineering, The Hebrew University, Jerusalem, Israel. nir@cs.huji.ac.il ido.amit@weizmann.ac.il. ; Department of Immunology, Weizmann Institute of Science, Rehovot, Israel. nir@cs.huji.ac.il ido.amit@weizmann.ac.il.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25103404" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Lineage/genetics ; Chromatin/*metabolism ; Chromatin Immunoprecipitation/methods ; *Enhancer Elements, Genetic ; Female ; Gene Expression Profiling ; *Gene Expression Regulation ; Hematopoiesis/*genetics ; Hematopoietic Stem Cells/cytology/*metabolism ; Histones/chemistry/metabolism ; Mice ; Transcription Factors/*metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
    ISSN: 1075-4261
    Keywords: DNA dyes ; single-stranded DNA ; oxazole yellow ; fluorescent dyes ; Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: Interactions between short single-stranded DNA oligomers of homogeneous base composition and the fluorescent probes oxazole yellow (YO) and its homodimer YOYO are described. The oligomers included 15-mers and 30-mers of polydA, polydT, polydG, and polydC. Interactions between the dyes and DNA hybrids formed from complementary homogeneous strands of equal length were also investigated. No interactions were observed between the dyes and the monomeric monophosphate nucleosides A, G, T, or C. The dyes were found to interact much more strongly with the purine oligomers polydA and polydG than with the pyrimidine oligomers polydT and polydC. PolydA of both lengths has strong interactions with YOYO, whereas the polydG 30-mer interacts strongly with monomeric YO. The 15-mers of polydG and polydC of both lengths show little interaction with either dye. Interactions of the dyes with the polydA/polydT and polydG/polydC hybrids tend to be dominated by interactions with polydA and polydG, respectively. Although dye interactions generally were facilitated by hybridization, particularly for polydA/polydT, the interactions were similar to those with the single strands and different from those that have been observed in long double-stranded DNA. © 1998 John Wiley & Sons, Inc. Biospectroscopy 4: 17-25, 1998
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0614
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract Three fungi Neocallimastix frontalis EB 188, Piromyces communis DC 193 and Orpinomyces ssp. RW 206, representing the predominant cultures isolated from cattle, were shown to respond to the addition of Aspergillus oryzae fermentation extract (i.e., Amaferm; BioZyme Inc., St. Joseph, Mo.) stimulation. Growth rates, protein and cellulase secretion and fungal mass production were all accelerated in the presence of the extract. Analysis of volatile fatty acids produced by these three species suggested that extract addition increased and altered gas production. Fractionation and preliminary analysis of the components present in the soluble extract, which stimulated the growth of the cellulolytic fungus N. frontalis EB 188, were also attempted. Soluble and filtered, sterilized extract was treated prior to use as a stimulant. Pretreatments included dialysis, ultraviolet irradiation, freeze thaw cycling, boiling, autoclaving, digestion with protease, autodigestion, organic extraction, decolorizing-carbon binding and polyethylene glycol concentration. Boiling, protease treatment, organic extraction, freeze thaw cycling and decolorizing-carbon binding reduced the ability of the extract to stimulate fungal cultures. Gel electrophoresis methods demonstrated that protein- and cellulasesecretion profiles were not identical in control and stimulated cultures. High-performance liquid chromatography methods allowed the separation of the extract into a limited number of ultraviolet-absorbing peaks, of which several stimulated the physiology of the fungus.
    Type of Medium: Electronic Resource
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