The Experts below are selected from a list of 3558 Experts worldwide ranked by ideXlab platform
J B Gurdon - One of the best experts on this subject based on the ideXlab platform.
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histone variant macroh2a confers resistance to Nuclear Reprogramming
The EMBO Journal, 2011Co-Authors: Vincent Pasque, J B Gurdon, Astrid Gillich, Nigel GarrettAbstract:How various layers of epigenetic repression restrict somatic cell Nuclear Reprogramming is poorly understood. The transfer of mammalian somatic cell nuclei into Xenopus oocytes induces transcriptional Reprogramming of previously repressed genes. Here, we address the mechanisms that restrict Reprogramming following Nuclear transfer by assessing the stability of the inactive X chromosome (Xi) in different stages of inactivation. We find that the Xi of mouse post‐implantation‐derived epiblast stem cells (EpiSCs) can be reversed by Nuclear transfer, while the Xi of differentiated or extraembryonic cells is irreversible by Nuclear transfer to oocytes. After Nuclear transfer, Xist RNA is lost from chromatin of the Xi. Most epigenetic marks such as DNA methylation and Polycomb‐deposited H3K27me3 do not explain the differences between reversible and irreversible Xi. Resistance to Reprogramming is associated with incorporation of the histone variant macroH2A, which is retained on the Xi of differentiated cells, but absent from the Xi of EpiSCs. Our results uncover the decreased stability of the Xi in EpiSCs, and highlight the importance of combinatorial epigenetic repression involving macroH2A in restricting transcriptional Reprogramming by oocytes. There is a [Have you seen?][1] (June 2011) associated with this Article. [1]: http://dx.doi.org/10.1038/emboj.2011.172
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from Nuclear transfer to Nuclear Reprogramming the reversal of cell differentiation
Annual Review of Cell and Developmental Biology, 2006Co-Authors: J B GurdonAbstract:This is a personal historical account of events leading from the earliest success in vertebrate Nuclear transfer to the current hope that Nuclear Reprogramming may facilitate cell replacement therapy. Early morphological evidence in Amphibia for the toti- or multipotentiality of some nuclei from differentiated cells first established the principle of the conservation of the genome during cell differentiation. Molecular markers show that many somatic cell nuclei are reprogrammed to an embryonic pattern of gene expression soon after Nuclear transplantation to eggs. The germinal vesicles of oocytes in first meiotic prophase have a direct Reprogramming activity on mammalian as well as amphibian nuclei and offer a route to identify Nuclear Reprogramming molecules. Amphibian eggs and oocytes have a truly remarkable ability to transcribe genes as DNA or nuclei, to translate mRNA, and to modify or localize proteins injected into them. The development of Nuclear transplant embryos depends on the ability of cells t...
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from intestine to muscle Nuclear Reprogramming through defective cloned embryos
Proceedings of the National Academy of Sciences of the United States of America, 2002Co-Authors: James A Byrne, Stina Simonsson, J B GurdonAbstract:Nuclear transplantation is one of the very few ways by which the genetic content and capacity for Nuclear Reprogramming can be assessed in individual cells of differentiated somatic tissues. No more than 6% of the cells of differentiated tissues have thus far been shown to have nuclei that can be reprogrammed to elicit the formation of unrelated cell types. In Amphibia, about 25% of such Nuclear transfers form morphologically abnormal partial blastulae that die within 24 h. We have investigated the genetic content and capacity for Reprogramming of those nuclei that generate partial blastulae, using as donors the intestinal epithelium cells of feeding Xenopus larvae. We have analyzed single Nuclear transplant embryos obtained directly from intestinal tissue, thereby avoiding any genetic or epigenetic changes that might accumulate during cell culture. The expression of the intestine-specific gene intestinal fatty acid binding protein is extinguished by at least 104 times, within a few hours of Nuclear transplantation. At the same time several genes that are normally expressed only in early embryos are very strongly activated in Nuclear transplant embryos, but to an unregulated extent. Remarkably, cells from intestine-derived partial blastulae, when grafted to normal host embryos, contribute to several host tissues and participate in the normal 100-fold increase in axial muscle over several months. Thus, cells of defective cloned embryos unable to survive for more than 1 day can be reprogrammed to participate in new directions of differentiation and to maintain indefinite growth, despite the abnormal expression of early genes.
John B. Gurdon - One of the best experts on this subject based on the ideXlab platform.
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Epigenetic memory in the context of Nuclear Reprogramming and cancer
Briefings in Functional Genomics, 2013Co-Authors: Richard P. Halley-stott, John B. GurdonAbstract:Epigenetic memory represents a natural mechanism whereby the identity of a cell is maintained through successive cell cycles, allowing the specification and maintenance of differentiation during development and in adult cells. Cancer is a loss or reversal of the stable differentiated state of adult cells and may be mediated in part by epigenetic changes. The identity of somatic cells can also be reversed experimentally by Nuclear Reprogramming. Nuclear Reprogramming experiments reveal the mechanisms required to activate embryonic gene expression in adult cells and thus provide insight into the reversal of epigenetic memory. In this article, we will introduce epigenetic memory and the mechanisms by which it may operate. We limit our discussion primarily to the context of Nuclear Reprogramming and briefly discuss the relevance of memory and Reprogramming to cancer biology.
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Nuclear Reprogramming
Development, 2013Co-Authors: Richard P. Halley-stott, Vincent Pasque, John B. GurdonAbstract:There is currently particular interest in the field of Nuclear Reprogramming, a process by which the identity of specialised cells may be changed, typically to an embryonic-like state. Reprogramming procedures provide insight into many mechanisms of fundamental cell biology and have several promising applications, most notably in healthcare through the development of human disease models and patient-specific tissue-replacement therapies. Here, we introduce the field of Nuclear Reprogramming and briefly discuss six of the procedures by which Reprogramming may be experimentally performed: Nuclear transfer to eggs or oocytes, cell fusion, extract treatment, direct Reprogramming to pluripotency and transdifferentiation.
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epigenetic factors influencing resistance to Nuclear Reprogramming
Trends in Genetics, 2011Co-Authors: John B. Gurdon, Vincent Pasque, Kei Miyamoto, Jerome Jullien, Richard P HalleystottAbstract:Patient-specific somatic cell Reprogramming is likely to have a large impact on medicine by providing a source of cells for disease modelling and regenerative medicine. Several strategies can be used to reprogram cells, yet they are generally characterised by a low Reprogramming efficiency, reflecting the remarkable stability of the differentiated state. Transcription factors, chromatin modifications, and noncoding RNAs can increase the efficiency of Reprogramming. However, the success of Nuclear Reprogramming is limited by epigenetic mechanisms that stabilise the state of gene expression in somatic cells and thereby resist efficient Reprogramming. We review here the factors that influence Reprogramming efficiency, especially those that restrict the natural Reprogramming mechanisms of eggs and oocytes. We see this as a step towards understanding the mechanisms by which Nuclear Reprogramming takes place.
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Histone variant macroH2A confers resistance to Nuclear Reprogramming
The EMBO Journal, 2011Co-Authors: Vincent Pasque, Astrid Gillich, Nigel Garrett, John B. GurdonAbstract:How various layers of epigenetic repression restrict somatic cell Nuclear Reprogramming is poorly understood. The transfer of mammalian somatic cell nuclei into Xenopus oocytes induces transcriptional Reprogramming of previously repressed genes. Here, we address the mechanisms that restrict Reprogramming following Nuclear transfer by assessing the stability of the inactive X chromosome (Xi) in different stages of inactivation. We find that the Xi of mouse post-implantation-derived epiblast stem cells (EpiSCs) can be reversed by Nuclear transfer, while the Xi of differentiated or extraembryonic cells is irreversible by Nuclear transfer to oocytes. After Nuclear transfer, Xist RNA is lost from chromatin of the Xi. Most epigenetic marks such as DNA methylation and Polycomb-deposited H3K27me3 do not explain the differences between reversible and irreversible Xi. Resistance to Reprogramming is associated with incorporation of the histone variant macroH2A, which is retained on the Xi of differentiated cells, but absent from the Xi of EpiSCs. Our results uncover the decreased stability of the Xi in EpiSCs, and highlight the importance of combinatorial epigenetic repression involving macroH2A in restricting transcriptional Reprogramming by oocytes.
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Efficiencies and Mechanisms of Nuclear Reprogramming
Cold Spring Harbor Symposia on Quantitative Biology, 2010Co-Authors: Vincent Pasque, Kei Miyamoto, John B. GurdonAbstract:The differentiated state of somatic cells is highly stable, but it can be experimentally reversed. The resulting cells can then be redirected into many different pathways. Nuclear Reprogramming has been achieved by Nuclear transfer to eggs, cell fusion, and overexpression of transcription factors. The mechanisms of Nuclear Reprogramming are not understood, but some insight into them is provided by comparing the efficiencies of different Reprogramming strategies. Here, we compare these efficiencies by describing the frequency and rapidity with which Reprogramming is induced and by the proportion of cells and level of expression in which Reprogramming is achieved. We comment on the mechanisms that lead to successful somatic-cell Reprogramming and on those that resist in helping to maintain the differentiated state of somatic cells.
Yong Zhang - One of the best experts on this subject based on the ideXlab platform.
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oocytes selected using bcb staining enhance Nuclear Reprogramming and the in vivo development of scnt embryos in cattle
PLOS ONE, 2012Co-Authors: Jianmin Su, Yongsheng Wang, Ruizhe Li, Qian Li, Fusheng Quan, Hui Peng, Yong ZhangAbstract:The selection of good quality oocytes is crucial for in vitro fertilization and somatic cloning. Brilliant cresyl blue (BCB) staining has been used for selection of oocytes from several mammalian species. However, the effects of differential oocyte selection by BCB staining on Nuclear Reprogramming and in vivo development of SCNT embryos are not well understood. Immature compact cumulus–oocyte complexes (COCs) were divided into control (not exposed to BCB), BCB+ (blue cytoplasm) and BCB− (colorless cytoplasm) groups. We found that BCB+ oocytes yielded a significantly higher somatic cell Nuclear transfer (SCNT) blastocyst rate and full term development rate of bovine SCNT embryos than the BCB− and control oocytes. BCB+ embryos (embryos developed from BCB+ oocytes) showed increased acetylation levels of histone H3 at K9 and K18 (AcH3K9, AcH3K18), and methylation levels of histone H3 at K4 (H3K4me2) than BCB− embryos (embryos developed from BCB− oocytes) at the two-cell stage. Furthermore, BCB+ embryos generated more total cells, trophectoderm (TE) cells, and inner cell mass (ICM) cells, and fewer apoptotic cells than BCB− embryos. The expression of SOX2, CDX2, and anti-apoptotic microRNA-21 were up-regulated in the BCB+ blastocysts compared with BCB− blastocysts, whereas the expression of pro-apoptotic gene Bax was down-regulated in BCB+ blastocysts. These results strongly suggest that BCB+ oocytes have a higher Nuclear Reprogramming capacity, and that BCB staining can be used to select developmentally competent oocytes for Nuclear transfer.
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scriptaid improves in vitro development and Nuclear Reprogramming of somatic cell Nuclear transfer bovine embryos
Cellular Reprogramming, 2011Co-Authors: Lijun Wang, Jianmin Su, Yongsheng Wang, Yanyan Li, Hui Zhang, Wenbing Xu, Xianrong Xiong, Yong ZhangAbstract:Abstract The present study evaluated the effect of Scriptaid, a novel histone deacetylase inhibitor (HDACi), on the in vitro development of somatic cell Nuclear transfer (SCNT) bovine embryos. Average fluorescence intensity of two epigenetic markers (H3K9ac and H3K9m2) at two-cell, eight-cell, and blastocyst stages, and the expression levels of two developmental important genes (Oct4 and IFN-t) at the blastocyst stage were also examined to assess the influence of Scriptaid on the Nuclear Reprogramming of bovine SCNT embryos. The results showed that treatment with 500 nM Scriptaid for 14 h after activation significantly increased the cleavage rate, blastocyst formation rate, and blastocyst hatching rate of SCNT embryos compared with those of nontreated counterparts, but the total number of blastomeres per blastocyst did not differ. Scriptaid treatment also significantly increased the immunofluorescent signal for H3K9ac in SCNT embryos at two-cell, eight-cell, and blastocyst stages, and the fluorescent sign...
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oxamflatin significantly improves Nuclear Reprogramming blastocyst quality and in vitro development of bovine scnt embryos
PLOS ONE, 2011Co-Authors: Jianmin Su, Yongsheng Wang, Yanyan Li, Ruizhe Li, Qian Li, Yongyan Wu, Fusheng Quan, Yong ZhangAbstract:Aberrant epigenetic Nuclear Reprogramming results in low somatic cloning efficiency. Altering epigenetic status by applying histone deacetylase inhibitors (HDACi) enhances developmental potential of somatic cell Nuclear transfer (SCNT) embryos. The present study was carried out to examine the effects of Oxamflatin, a novel HDACi, on the Nuclear Reprogramming and development of bovine SCNT embryos in vitro. We found that Oxamflatin modified the acetylation status on H3K9 and H3K18, increased total and inner cell mass (ICM) cell numbers and the ratio of ICM∶trophectoderm (TE) cells, reduced the rate of apoptosis in SCNT blastocysts, and significantly enhanced the development of bovine SCNT embryos in vitro. Furthermore, Oxamflatin treatment suppressed expression of the pro-apoptotic gene Bax and stimulated expression of the anti-apoptotic gene Bcl-XL and the pluripotency-related genes OCT4 and SOX2 in SCNT blastocysts. Additionally, the treatment also reduced the DNA methylation level of satellite I in SCNT blastocysts. In conclusion, Oxamflatin modifies epigenetic status and gene expression, increases blastocyst quality, and subsequently enhances the Nuclear Reprogramming and developmental potential of SCNT embryos.
Vincent Pasque - One of the best experts on this subject based on the ideXlab platform.
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Nuclear Reprogramming
Development, 2013Co-Authors: Richard P. Halley-stott, Vincent Pasque, John B. GurdonAbstract:There is currently particular interest in the field of Nuclear Reprogramming, a process by which the identity of specialised cells may be changed, typically to an embryonic-like state. Reprogramming procedures provide insight into many mechanisms of fundamental cell biology and have several promising applications, most notably in healthcare through the development of human disease models and patient-specific tissue-replacement therapies. Here, we introduce the field of Nuclear Reprogramming and briefly discuss six of the procedures by which Reprogramming may be experimentally performed: Nuclear transfer to eggs or oocytes, cell fusion, extract treatment, direct Reprogramming to pluripotency and transdifferentiation.
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epigenetic factors influencing resistance to Nuclear Reprogramming
Trends in Genetics, 2011Co-Authors: John B. Gurdon, Vincent Pasque, Kei Miyamoto, Jerome Jullien, Richard P HalleystottAbstract:Patient-specific somatic cell Reprogramming is likely to have a large impact on medicine by providing a source of cells for disease modelling and regenerative medicine. Several strategies can be used to reprogram cells, yet they are generally characterised by a low Reprogramming efficiency, reflecting the remarkable stability of the differentiated state. Transcription factors, chromatin modifications, and noncoding RNAs can increase the efficiency of Reprogramming. However, the success of Nuclear Reprogramming is limited by epigenetic mechanisms that stabilise the state of gene expression in somatic cells and thereby resist efficient Reprogramming. We review here the factors that influence Reprogramming efficiency, especially those that restrict the natural Reprogramming mechanisms of eggs and oocytes. We see this as a step towards understanding the mechanisms by which Nuclear Reprogramming takes place.
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histone variant macroh2a confers resistance to Nuclear Reprogramming
The EMBO Journal, 2011Co-Authors: Vincent Pasque, J B Gurdon, Astrid Gillich, Nigel GarrettAbstract:How various layers of epigenetic repression restrict somatic cell Nuclear Reprogramming is poorly understood. The transfer of mammalian somatic cell nuclei into Xenopus oocytes induces transcriptional Reprogramming of previously repressed genes. Here, we address the mechanisms that restrict Reprogramming following Nuclear transfer by assessing the stability of the inactive X chromosome (Xi) in different stages of inactivation. We find that the Xi of mouse post‐implantation‐derived epiblast stem cells (EpiSCs) can be reversed by Nuclear transfer, while the Xi of differentiated or extraembryonic cells is irreversible by Nuclear transfer to oocytes. After Nuclear transfer, Xist RNA is lost from chromatin of the Xi. Most epigenetic marks such as DNA methylation and Polycomb‐deposited H3K27me3 do not explain the differences between reversible and irreversible Xi. Resistance to Reprogramming is associated with incorporation of the histone variant macroH2A, which is retained on the Xi of differentiated cells, but absent from the Xi of EpiSCs. Our results uncover the decreased stability of the Xi in EpiSCs, and highlight the importance of combinatorial epigenetic repression involving macroH2A in restricting transcriptional Reprogramming by oocytes. There is a [Have you seen?][1] (June 2011) associated with this Article. [1]: http://dx.doi.org/10.1038/emboj.2011.172
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Histone variant macroH2A confers resistance to Nuclear Reprogramming
The EMBO Journal, 2011Co-Authors: Vincent Pasque, Astrid Gillich, Nigel Garrett, John B. GurdonAbstract:How various layers of epigenetic repression restrict somatic cell Nuclear Reprogramming is poorly understood. The transfer of mammalian somatic cell nuclei into Xenopus oocytes induces transcriptional Reprogramming of previously repressed genes. Here, we address the mechanisms that restrict Reprogramming following Nuclear transfer by assessing the stability of the inactive X chromosome (Xi) in different stages of inactivation. We find that the Xi of mouse post-implantation-derived epiblast stem cells (EpiSCs) can be reversed by Nuclear transfer, while the Xi of differentiated or extraembryonic cells is irreversible by Nuclear transfer to oocytes. After Nuclear transfer, Xist RNA is lost from chromatin of the Xi. Most epigenetic marks such as DNA methylation and Polycomb-deposited H3K27me3 do not explain the differences between reversible and irreversible Xi. Resistance to Reprogramming is associated with incorporation of the histone variant macroH2A, which is retained on the Xi of differentiated cells, but absent from the Xi of EpiSCs. Our results uncover the decreased stability of the Xi in EpiSCs, and highlight the importance of combinatorial epigenetic repression involving macroH2A in restricting transcriptional Reprogramming by oocytes.
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Efficiencies and Mechanisms of Nuclear Reprogramming
Cold Spring Harbor Symposia on Quantitative Biology, 2010Co-Authors: Vincent Pasque, Kei Miyamoto, John B. GurdonAbstract:The differentiated state of somatic cells is highly stable, but it can be experimentally reversed. The resulting cells can then be redirected into many different pathways. Nuclear Reprogramming has been achieved by Nuclear transfer to eggs, cell fusion, and overexpression of transcription factors. The mechanisms of Nuclear Reprogramming are not understood, but some insight into them is provided by comparing the efficiencies of different Reprogramming strategies. Here, we compare these efficiencies by describing the frequency and rapidity with which Reprogramming is induced and by the proportion of cells and level of expression in which Reprogramming is achieved. We comment on the mechanisms that lead to successful somatic-cell Reprogramming and on those that resist in helping to maintain the differentiated state of somatic cells.
Andre Terzic - One of the best experts on this subject based on the ideXlab platform.
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Metabolome and metaboproteome remodeling in Nuclear Reprogramming.
Cell Cycle, 2013Co-Authors: Clifford D.l. Folmes, D. Kent Arrell, Jelena Zlatkovic‐lindor, Almudena Martinez-fernandez, Carmen Perez-terzic, Timothy J. Nelson, Andre TerzicAbstract:Nuclear Reprogramming resets differentiated tissue to generate induced pluripotent stem (iPS) cells. While genomic attributes underlying reacquisition of the embryonic-like state have been delineated, less is known regarding the metabolic dynamics underscoring induction of pluripotency. Metabolomic profiling of fibroblasts vs. iPS cells demonstrated Nuclear Reprogramming-associated induction of glycolysis, realized through augmented utilization of glucose and accumulation of lactate. Real-time assessment unmasked downregulated mitochondrial reserve capacity and ATP turnover correlating with pluripotent induction. Reduction in oxygen consumption and acceleration of extracellular acidification rates represent high-throughput markers of the transition from oxidative to glycolytic metabolism, characterizing stemness acquisition. The bioenergetic transition was supported by proteome remodeling, whereby 441 proteins were altered between fibroblasts and derived iPS cells. Systems analysis revealed overrepresente...
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Nuclear Reprogramming with c-Myc Potentiates Glycolytic Capacity of Derived Induced Pluripotent Stem Cells
Journal of Cardiovascular Translational Research, 2013Co-Authors: Clifford D.l. Folmes, Almudena Martinez-fernandez, Carmen Perez-terzic, Timothy J. Nelson, Randolph S. Faustino, Satsuki Yamada, Andre TerzicAbstract:Reprogramming strategies influence the differentiation capacity of derived induced pluripotent stem (iPS) cells. Removal of the Reprogramming factor c-Myc reduces tumorigenic incidence and increases cardiogenic potential of iPS cells. c-Myc is a regulator of energy metabolism, yet the impact on metabolic Reprogramming underlying pluripotent induction is unknown. Here, mitochondrial and metabolic interrogation of iPS cells derived with (4F) and without (3F) c-Myc demonstrated that Nuclear Reprogramming consistently reverted mitochondria to embryonic-like immature structures. Metabolomic profiling segregated derived iPS cells from the parental somatic source based on the attained pluripotency-associated glycolytic phenotype and discriminated between 3F versus 4F clones based upon glycolytic intermediates. Real-time flux analysis demonstrated a greater glycolytic capacity in 4F iPS cells, in the setting of equivalent oxidative capacity to 3F iPS cells. Thus, inclusion of c-Myc potentiates the pluripotent glycolytic behavior of derived iPS cells, supporting c-Myc-free Reprogramming as a strategy to facilitate oxidative metabolism-dependent lineage engagement.
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Energy metabolism in Nuclear Reprogramming
Biomarkers in Medicine, 2011Co-Authors: Clifford D.l. Folmes, Timothy J. Nelson, Andre TerzicAbstract:Nuclear Reprogramming with stemness factors enables resetting of somatic differentiated tissue back to the pluripotent ground state. Recent evidence implicates mitochondrial restructuring and bioenergetic plasticity as key components underlying execution of orchestrated dedifferentiation and derivation of induced pluripotent stem cells. Aerobic to anaerobic transition of somatic oxidative energy metabolism into a glycolytic metabotype promotes proficient Reprogramming, establishing a novel regulator of acquired stemness. Metabolomic profiling has further identified specific metabolic remodeling traits defining lineage redifferentiation of pluripotent cells. Therefore, mitochondrial biogenesis and energy metabolism comprise a vital axis for biomarker discovery, intimately reflecting the molecular dynamics fundamental for the resetting and redirection of cell fate.
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somatic oxidative bioenergetics transitions into pluripotency dependent glycolysis to facilitate Nuclear Reprogramming
Cell Metabolism, 2011Co-Authors: Clifford D.l. Folmes, Timothy J. Nelson, Almudena Martinezfernandez, Yasuhiro Ikeda, Kent D Arrell, Jelena Zlatkovic Lindor, Petras P Dzeja, Carmen Perezterzic, Andre TerzicAbstract:Summary The bioenergetics of somatic dedifferentiation into induced pluripotent stem cells remains largely unknown. Here, stemness factor-mediated Nuclear Reprogramming reverted mitochondrial networks into cristae-poor structures. Metabolomic footprinting and fingerprinting distinguished derived pluripotent progeny from parental fibroblasts according to elevated glucose utilization and production of glycolytic end products. Temporal sampling demonstrated glycolytic gene potentiation prior to induction of pluripotent markers. Functional metamorphosis of somatic oxidative phosphorylation into acquired pluripotent glycolytic metabolism conformed to an embryonic-like archetype. Stimulation of glycolysis promoted, while blockade of glycolytic enzyme activity blunted, Reprogramming efficiency. Metaboproteomics resolved upregulated glycolytic enzymes and downregulated electron transport chain complex I subunits underlying cell fate determination. Thus, the energetic infrastructure of somatic cells transitions into a required glycolytic metabotype to fuel induction of pluripotency.
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Nuclear Reprogramming Strategy Modulates Differentiation Potential of Induced Pluripotent Stem Cells
Journal of Cardiovascular Translational Research, 2011Co-Authors: Almudena Martinez-fernandez, Timothy J. Nelson, Andre TerzicAbstract:Bioengineered by ectopic expression of stemness factors, induced pluripotent stem (iPS) cells demonstrate embryonic stem cell-like properties and offer a unique platform for derivation of autologous pluripotent cells from somatic tissue sources. In the process of Nuclear Reprogramming, somatic tissues are converted to a pluripotent ground state, thus unlocking an unlimited potential to expand progenitor pools. Molecular dissection of Nuclear Reprogramming suggests that a residual memory derived from the original parental source, along with the remnants of the Reprogramming process itself, leads to a biased potential of the bioengineered progeny to differentiate into target tissues such as cardiac cytotypes. In this way, iPS cells that fulfill pluripotency criteria may display heterogeneous profiles for lineage specification. Small molecule-based strategies have been identified that modulate the epigenetic state of reprogrammed cells and are optimized to erase the residual memory and homogenize the differentiation potential of iPS cells derived from distinct backgrounds. Here, we describe the salient components of the Reprogramming process and their effect on the downstream differentiation capacity of the iPS populations in the context of cardiovascular regenerative applications.
