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Temporal epigenetic modifications differentially regulate ES cell-like colony formation and maturation

Stem Cell Discovery 2012年第2期2卷 45-57页

作者： Jong S. Rim Karen L. Strickler christian w. barnes Lettie L. Harkins Jaroslaw.Staszkiew.cz Jeffrey M. Gimble Gregory H. Leno Kenneth J. Eilertsen Department of Anatomy & Cell Biology Carver College of Medicine University of Iowa Iowa City USA NuPotential Inc. Baton Rouge USA Stem Cell Biology Laboratory Pennington Biomedical Research Center Baton Rouge USA

Human somatic cells can be directly reprogrammed to induced pluripotent stem (iPS) cells by forced expression of the transcription factors Oct4, Sox2, and either Klf4 and cMyc or Nanog and Lin28, using virus-based systems. How.ver, low.reprogramming efficiency and the potential for deleterious virus-induced genomic modification limit the clinical potential of this technology. Recent reports indicate, how.ver, that the generation of iPS cells can be enhanced by the addition of synthetic small molecules, including epigenetic modulators. In this report, w. demonstrate that the epigenetic modifiers Valproic Acid (VPA) and 5-azacytidine activate the reciprocal transcriptional regulation of endogenous pluripotency transcription factor genes in human dermal fibroblasts and that VPA alone can directly activate endogenous Oct4 in the absence of transgenes. Moreover, using human adipose cells, w. demonstrate that histone deacetylase inhibition, prior to reprogramming factor transfection, increases embryonic stem (ES) cell-like colony formation ~2 - 3 fold. In addition, DNA methyltransferase (DNMT) inhibition during human ES cell culture promotes maturation of reprogrammed somatic cells, increasing the yield ~4 fold. These data provide proof of principle that reprogramming efficiency can be improved by inhibiting specific repressive epigenetic regulatory components at the levels of ES cell-like colony formation and maturation. In addition, these studies raise the interesting possibility that a more efficient small molecule-based reprogramming system may provide a superior alternative to current virus-based approaches.

关键词： Epigenetic Modification Somatic Cell Reprogramming

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Reprogramming mouse ear mesenchymal stem cells (EMSC) expressing the Dlk1-Dio3 imprinted gene cluster

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Stem Cell Discovery 2013年第1期3卷 64-71页

作者： Ru Gao Jong S. Rim Karen L. Strickler christian w. barnes Lettie L. Harkins Jaroslaw.Staszkiew.cz Jeffery M. Gimble Barbara Gaw.onska-Kozak Gregory H. Leno Kenneth J. Eilertsen Department of Anatomy & Cell Biology Carver College of Medicine University of Iowa Iowa City USA Institute of Animal Reproduction and Food Research of Polish Academy of Sciences Olsztyn Poland NuPotential Inc. Baton Rouge USA Stem Cell Biology Laboratory Pennington Biomedical Research Center Baton Rouge USA

The identification of a single, early marker for full developmental potential of induced pluripotent stem (iPS) cells has proven elusive. Recently, how.ver, activation of the imprinted gene cluster, Dlk1-Dio3 has emerged as a viable candidate in the mouse. To explore the relationship betw.en Dlk1-Dio3 expression and developmental potential more fully, w. used murine ear mesenchymal stem cells (mEMSC) for iPS cell induction. Mouse EMSC are easily obtained and share functional characteristics w.th embryonic stem (ES) cells and therefore, may be a reliable non-embryonic source for iPS cell production. w. report that mEMSC express high levels of Gtl2, a maternally expressed gene w.thin the Dlk1-Dio3 imprinted cluster. Moreover, mEMSC produce Gtl2 expressing (Gtl2on) iPSC clones that share functional characteristics w.th ES cell clones. The production of Gtl2on iPS cell clones from mEMSC provides a new.model w.th w.ich to investigate the regulation of Dlk1-Dio3 cluster activity during direct cell reprogramming.

关键词： iPSCs Reprogramming Pluripotent Stem Cell

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Geochemical CompGeochemical Comparison of Fresh and w.athered Tailings from the Sabodala Gold Mine Kedougou Region, Senegal Follow.ng 6 Years of Operationarison of Fresh and w.athered Tailings from the Sabodala Gold Mine Kedougou Region, Senegal Follow.ng 6 Years of Operation

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Journal of Geoscience and Environment Protection 2020年第7期8卷 177-194页

作者： Ibrahima Dia Mababa Diagne Mamadou Gueye Andrew.barnes christian Mace Earth Sciences Institute Cheikh Anta Diop University Dakar Senegal Geochemic Ltd. Monmouthshire United Kingdom Teranga Gold Corporation Toronto Canada

The Sabodala gold mine is located in the Kedegou region in eastern Senegal near the border w.th Mali in a tropical Savannah climate zone w.th distinct w.t and dry seasons. The mine has been operating since 2009 w.th active tailings deposition giving an ideal opportunity to study the w.athering characteristics of carbonate rich tailings materials under real w.rld conditions. The mine is operated in accordance w.th international best practice w.th regular monitoring of w.ter quality and tailings chemistry in accordance w.th the international cyanide management code (ICMC) and also in order to monitor and control any potential impacts from Acid Rock Drainage and Metal Leaching (ARDML) that may be generated from the tailings materials and w.ste rock. In 2015 as part of a project looking at the potential for re-use of generated tailings as construction materials, a number of additional geochemical tests including w.ole rock assays, mineralogy, Acid Base Accounting in accordance w.th modified Sobek method w.th siderite correction, together w.th paste pH and electrical conductivity (Ec) measurements w.re undertaken. The purpose of the study w.s to update the predictions of the potential for ARDML generation and drainage pH in leachates forming from the Sabodala tailings. The tests w.re run on one composite w.athered and 3 selective fresh samples collected by auger drilling on three holes over the tailing. Results have enabled a better understanding of the chemical w.athering characteristics of finely ground tailings materials under tropical w.athering conditions and the nature of secondary minerals precipitated.

关键词： Acid Base Accounting Neutralization Potential Elemental Analysis Mineralogy

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