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        Direct reprogramming of human neural stem cells by OCT4

        Kim, Jeong Beom,Greber, Boris,Araú,zo-Bravo, Marcos J.,Meyer, Johann,Park, Kook In,Zaehres, Holm,Schö,ler, Hans R. Macmillan Publishers Limited. All rights reserved 2009 Nature Vol.461 No.7264

        Induced pluripotent stem (iPS) cells have been generated from mouse and human somatic cells by ectopic expression of four transcription factors (OCT4 (also called POU5F1), SOX2, c-Myc and KLF4). We previously reported that Oct4 alone is sufficient to reprogram directly adult mouse neural stem cells to iPS cells. Here we report the generation of one-factor human iPS cells from human fetal neural stem cells (one-factor (1F) human NiPS cells) by ectopic expression of OCT4 alone. One-factor human NiPS cells resemble human embryonic stem cells in global gene expression profiles, epigenetic status, as well as pluripotency in vitro and in vivo. These findings demonstrate that the transcription factor OCT4 is sufficient to reprogram human neural stem cells to pluripotency. One-factor iPS cell generation will advance the field further towards understanding reprogramming and generating patient-specific pluripotent stem cells.

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        Reading and writing single-atom magnets

        Natterer, Fabian D.,Yang, Kai,Paul, William,Willke, Philip,Choi, Taeyoung,Greber, Thomas,Heinrich, Andreas J.,Lutz, Christopher P. Macmillan Publishers Limited, part of Springer Nat 2017 Nature Vol.543 No.7644

        <P>The single-atom bit represents the ultimate limit of the classical approach to high-density magnetic storage media. So far, the smallest individually addressable bistable magnetic bits have consisted of 3-12 atoms(1-3). Long magnetic relaxation times have been demonstrated for single lanthanide atoms in molecular magnets(4-12), for lanthanides diluted in bulk crystals(13), and recently for ensembles of holmium (Ho) atoms supported on magnesium oxide (MgO)(14). These experiments suggest a path towards data storage at the atomic limit, but the way in which individual magnetic centres are accessed remains unclear. Here we demonstrate the reading and writing of the magnetism of individual Ho atoms on MgO, and show that they independently retain their magnetic information over many hours. We read the Ho states using tunnel magnetoresistance(15,16) and write the states with current pulses using a scanning tunnelling microscope. The magnetic origin of the long-lived states is confirmed by single-atom electron spin resonance(17) on a nearby iron sensor atom, which also shows that Ho has a large out-of-plane moment of 10.1 +/- 0.1 Bohr magnetons on this surface. To demonstrate independent reading and writing, we built an atomic-scale structure with two Ho bits, to which we write the four possible states and which we read out both magnetoresistively and remotely by electron spin resonance. The high magnetic stability combined with electrical reading and writing shows that single-atom magnetic memory is indeed possible.</P>

      • Direct Reprogramming of Fibroblasts into Neural Stem Cells by Defined Factors

        Han, D.,Tapia, N.,Hermann, A.,Hemmer, K.,Hoing, S.,Arauzo-Bravo, Marcos J.,Zaehres, H.,Wu, G.,Frank, S.,Moritz, S.,Greber, B.,Yang, J.,Lee, H.,Schwamborn, Jens C.,Storch, A.,Scholer, Hans R. Cell Press 2012 Cell stem cell Vol.10 No.4

        Recent studies have shown that defined sets of transcription factors can directly reprogram differentiated somatic cells to a different differentiated cell type without passing through a pluripotent state, but the restricted proliferative and lineage potential of the resulting cells limits the scope of their potential applications. Here we show that a combination of transcription factors (Brn4/Pou3f4, Sox2, Klf4, c-Myc, plus E47/Tcf3) induces mouse fibroblasts to directly acquire a neural stem cell identity-which we term as induced neural stem cells (iNSCs). Direct reprogramming of fibroblasts into iNSCs is a gradual process in which the donor transcriptional program is silenced over time. iNSCs exhibit cell morphology, gene expression, epigenetic features, differentiation potential, and self-renewing capacity, as well as in vitro and in vivo functionality similar to those of wild-type NSCs. We conclude that differentiated cells can be reprogrammed directly into specific somatic stem cell types by defined sets of specific transcription factors.

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