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  • 1
    Publication Date: 2010-10-22
    Description: Two forms of X-chromosome inactivation (XCI) ensure the selective silencing of female sex chromosomes during mouse embryogenesis. Imprinted XCI begins with the detection of Xist RNA expression on the paternal X chromosome (Xp) at about the four-cell stage of embryonic development. In the embryonic tissues of the inner cell mass, a random form of XCI occurs in blastocysts that inactivates either Xp or the maternal X chromosome (Xm). Both forms of XCI require the non-coding Xist RNA that coats the inactive X chromosome from which it is expressed. Xist has crucial functions in the silencing of X-linked genes, including Rnf12 (refs 3, 4) encoding the ubiquitin ligase RLIM (RING finger LIM-domain-interacting protein). Here we show, by targeting a conditional knockout of Rnf12 to oocytes where RLIM accumulates to high levels, that the maternal transmission of the mutant X chromosome (Deltam) leads to lethality in female embryos as a result of defective imprinted XCI. We provide evidence that in Deltam female embryos the initial formation of Xist clouds and Xp silencing are inhibited. In contrast, embryonic stem cells lacking RLIM are able to form Xist clouds and silence at least some X-linked genes during random XCI. These results assign crucial functions to the maternal deposit of Rnf12/RLIM for the initiation of imprinted XCI.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2967734/" 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/PMC2967734/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shin, Jongdae -- Bossenz, Michael -- Chung, Young -- Ma, Hong -- Byron, Meg -- Taniguchi-Ishigaki, Naoko -- Zhu, Xiaochun -- Jiao, Baowei -- Hall, Lisa L -- Green, Michael R -- Jones, Stephen N -- Hermans-Borgmeyer, Irm -- Lawrence, Jeanne B -- Bach, Ingolf -- 5 P30 DK32520/DK/NIDDK NIH HHS/ -- DK32520/DK/NIDDK NIH HHS/ -- GM053234/GM/NIGMS NIH HHS/ -- R01 CA131158/CA/NCI NIH HHS/ -- R01 CA131158-04/CA/NCI NIH HHS/ -- R01 GM033977/GM/NIGMS NIH HHS/ -- R01 GM053234/GM/NIGMS NIH HHS/ -- R01CA131158/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2010 Oct 21;467(7318):977-81. doi: 10.1038/nature09457.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Program in Gene Function and Expression, University of Massachusetts Medical School (UMMS), Worcester, Massachusetts 01605, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20962847" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Animals, Congenic ; Blastocyst/metabolism ; Cell Line ; Chromosomes, Mammalian/*genetics ; Embryo Loss/genetics ; Fathers ; Female ; Gene Silencing ; *Genomic Imprinting ; Male ; Mice ; Mice, Transgenic ; *Mothers ; RNA, Long Noncoding ; RNA, Untranslated/genetics ; Repressor Proteins/deficiency/genetics/*metabolism ; Ubiquitin-Protein Ligases ; X Chromosome/*genetics ; X Chromosome Inactivation/*genetics
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  • 2
    Publication Date: 2009-08-28
    Description: Mitochondria are found in all eukaryotic cells and contain their own genome (mitochondrial DNA or mtDNA). Unlike the nuclear genome, which is derived from both the egg and sperm at fertilization, the mtDNA in the embryo is derived almost exclusively from the egg; that is, it is of maternal origin. Mutations in mtDNA contribute to a diverse range of currently incurable human diseases and disorders. To establish preclinical models for new therapeutic approaches, we demonstrate here that the mitochondrial genome can be efficiently replaced in mature non-human primate oocytes (Macaca mulatta) by spindle-chromosomal complex transfer from one egg to an enucleated, mitochondrial-replete egg. The reconstructed oocytes with the mitochondrial replacement were capable of supporting normal fertilization, embryo development and produced healthy offspring. Genetic analysis confirmed that nuclear DNA in the three infants born so far originated from the spindle donors whereas mtDNA came from the cytoplast donors. No contribution of spindle donor mtDNA was detected in offspring. Spindle replacement is shown here as an efficient protocol replacing the full complement of mitochondria in newly generated embryonic stem cell lines. This approach may offer a reproductive option to prevent mtDNA disease transmission in affected families.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2774772/" 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/PMC2774772/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tachibana, Masahito -- Sparman, Michelle -- Sritanaudomchai, Hathaitip -- Ma, Hong -- Clepper, Lisa -- Woodward, Joy -- Li, Ying -- Ramsey, Cathy -- Kolotushkina, Olena -- Mitalipov, Shoukhrat -- P01 HD047675/HD/NICHD NIH HHS/ -- P01 HD047675-01A17045/HD/NICHD NIH HHS/ -- P01 HD047675-04/HD/NICHD NIH HHS/ -- P51 RR000163/RR/NCRR NIH HHS/ -- P51 RR000163-486766/RR/NCRR NIH HHS/ -- P51 RR000163-486775/RR/NCRR NIH HHS/ -- P51 RR000163-486819/RR/NCRR NIH HHS/ -- P51 RR000163-496038/RR/NCRR NIH HHS/ -- P51 RR000163-496045/RR/NCRR NIH HHS/ -- P51 RR000163-496074/RR/NCRR NIH HHS/ -- P51 RR000163-496133/RR/NCRR NIH HHS/ -- P51 RR000163-496134/RR/NCRR NIH HHS/ -- P51 RR000163-496136/RR/NCRR NIH HHS/ -- P51 RR000163-496137/RR/NCRR NIH HHS/ -- R01 HD057121/HD/NICHD NIH HHS/ -- R01 HD057121-01A2/HD/NICHD NIH HHS/ -- R01 NS044330/NS/NINDS NIH HHS/ -- R01 NS044330-05/NS/NINDS NIH HHS/ -- R24 RR013632/RR/NCRR NIH HHS/ -- R24 RR013632-10/RR/NCRR NIH HHS/ -- England -- Nature. 2009 Sep 17;461(7262):367-72. doi: 10.1038/nature08368. Epub 2009 Aug 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Oregon National Primate Research Center, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19710649" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Nucleus/genetics ; DNA, Mitochondrial/analysis/*genetics ; Embryo Transfer ; Embryonic Stem Cells/*cytology/*metabolism/transplantation ; Female ; Fertilization in Vitro ; Genes, Mitochondrial/*genetics ; Genome, Mitochondrial/*genetics ; Macaca mulatta/embryology/*genetics ; Male ; Meiosis ; Mitochondrial Diseases/genetics/prevention & control ; Mutation ; Oocytes/cytology/metabolism ; Pregnancy ; *Reproductive Techniques, Assisted
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  • 3
    Publication Date: 2012-10-30
    Description: Mutations in mitochondrial DNA (mtDNA) are associated with severe human diseases and are maternally inherited through the egg's cytoplasm. Here we investigated the feasibility of mtDNA replacement in human oocytes by spindle transfer (ST; also called spindle-chromosomal complex transfer). Of 106 human oocytes donated for research, 65 were subjected to reciprocal ST and 33 served as controls. Fertilization rate in ST oocytes (73%) was similar to controls (75%); however, a significant portion of ST zygotes (52%) showed abnormal fertilization as determined by an irregular number of pronuclei. Among normally fertilized ST zygotes, blastocyst development (62%) and embryonic stem cell isolation (38%) rates were comparable to controls. All embryonic stem cell lines derived from ST zygotes had normal euploid karyotypes and contained exclusively donor mtDNA. The mtDNA can be efficiently replaced in human oocytes. Although some ST oocytes displayed abnormal fertilization, remaining embryos were capable of developing to blastocysts and producing embryonic stem cells similar to controls.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3561483/" 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/PMC3561483/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tachibana, Masahito -- Amato, Paula -- Sparman, Michelle -- Woodward, Joy -- Sanchis, Dario Melguizo -- Ma, Hong -- Gutierrez, Nuria Marti -- Tippner-Hedges, Rebecca -- Kang, Eunju -- Lee, Hyo-Sang -- Ramsey, Cathy -- Masterson, Keith -- Battaglia, David -- Lee, David -- Wu, Diana -- Jensen, Jeffrey -- Patton, Phillip -- Gokhale, Sumita -- Stouffer, Richard -- Mitalipov, Shoukhrat -- 8P51OD011092/OD/NIH HHS/ -- EY021214/EY/NEI NIH HHS/ -- HD057121/HD/NICHD NIH HHS/ -- HD059946/HD/NICHD NIH HHS/ -- HD063276/HD/NICHD NIH HHS/ -- P51 OD011092/OD/NIH HHS/ -- P51 RR000163/RR/NCRR NIH HHS/ -- R01 EY021214/EY/NEI NIH HHS/ -- R01 HD057121/HD/NICHD NIH HHS/ -- R01 HD059946/HD/NICHD NIH HHS/ -- R01 HD063276/HD/NICHD NIH HHS/ -- England -- Nature. 2013 Jan 31;493(7434):627-31. doi: 10.1038/nature11647. Epub 2012 Oct 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Reproductive & Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, 505 NW 185th Avenue, Beaverton, Oregon 97006, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23103867" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Animals ; Cell Nucleus/genetics ; Cryopreservation ; Cytoplasm/genetics ; DNA, Mitochondrial/analysis/genetics ; Embryo, Mammalian/embryology ; Embryonic Stem Cells/cytology ; Female ; Fertilization ; *Genetic Therapy ; Humans ; Macaca mulatta/genetics/growth & development ; Microsatellite Repeats/genetics ; Mitochondrial Diseases/*genetics/*therapy ; Nuclear Transfer Techniques/*standards ; Oocytes/cytology ; Pregnancy ; Young Adult ; Zygote/cytology/pathology
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  • 4
    Publication Date: 2013-12-18
    Description: Strigolactones (SLs) are a group of newly identified plant hormones that control plant shoot branching. SL signalling requires the hormone-dependent interaction of DWARF 14 (D14), a probable candidate SL receptor, with DWARF 3 (D3), an F-box component of the Skp-Cullin-F-box (SCF) E3 ubiquitin ligase complex. Here we report the characterization of a dominant SL-insensitive rice (Oryza sativa) mutant dwarf 53 (d53) and the cloning of D53, which encodes a substrate of the SCF(D3) ubiquitination complex and functions as a repressor of SL signalling. Treatments with GR24, a synthetic SL analogue, cause D53 degradation via the proteasome in a manner that requires D14 and the SCF(D3) ubiquitin ligase, whereas the dominant form of D53 is resistant to SL-mediated degradation. Moreover, D53 can interact with transcriptional co-repressors known as TOPLESS-RELATED PROTEINS. Our results suggest a model of SL signalling that involves SL-dependent degradation of the D53 repressor mediated by the D14-D3 complex.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jiang, Liang -- Liu, Xue -- Xiong, Guosheng -- Liu, Huihui -- Chen, Fulu -- Wang, Lei -- Meng, Xiangbing -- Liu, Guifu -- Yu, Hong -- Yuan, Yundong -- Yi, Wei -- Zhao, Lihua -- Ma, Honglei -- He, Yuanzheng -- Wu, Zhongshan -- Melcher, Karsten -- Qian, Qian -- Xu, H Eric -- Wang, Yonghong -- Li, Jiayang -- England -- Nature. 2013 Dec 19;504(7480):401-5. doi: 10.1038/nature12870. Epub 2013 Dec 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] State Key Laboratory of Plant Genomics and National Center for Plant Gene Research (Beijing), Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China [2]. ; State Key Laboratory of Plant Genomics and National Center for Plant Gene Research (Beijing), Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China. ; VARI-SIMM Center, Center for Structure and Function of Drug Targets, CAS-Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. ; Laboratory of Structural Sciences, Van Andel Research Institute, 333 Bostwick Avenue Northeast, Grand Rapids, Michigan 49503, USA. ; State Key Laboratory of Rice Biology, China National Rice Research Institute, Chinese Academy of Agricultural Sciences, Hangzhou 310006, China. ; 1] VARI-SIMM Center, Center for Structure and Function of Drug Targets, CAS-Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China [2] Laboratory of Structural Sciences, Van Andel Research Institute, 333 Bostwick Avenue Northeast, Grand Rapids, Michigan 49503, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24336200" target="_blank"〉PubMed〈/a〉
    Keywords: Cloning, Molecular ; Gene Expression Regulation, Plant ; Lactones/*antagonists & inhibitors/*metabolism ; Models, Biological ; Multiprotein Complexes/chemistry/metabolism ; Mutation/genetics ; Oryza/genetics/*metabolism ; Plant Growth Regulators/antagonists & inhibitors/*metabolism ; Plant Proteins/chemistry/genetics/*metabolism ; Proteasome Endopeptidase Complex/metabolism ; Protein Binding ; Proteolysis ; *Signal Transduction ; Ubiquitin/metabolism
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  • 5
    Publication Date: 2014-03-29
    Description: Successful mammalian cloning using somatic cell nuclear transfer (SCNT) into unfertilized, metaphase II (MII)-arrested oocytes attests to the cytoplasmic presence of reprogramming factors capable of inducing totipotency in somatic cell nuclei. However, these poorly defined maternal factors presumably decline sharply after fertilization, as the cytoplasm of pronuclear-stage zygotes is reportedly inactive. Recent evidence suggests that zygotic cytoplasm, if maintained at metaphase, can also support derivation of embryonic stem (ES) cells after SCNT, albeit at low efficiency. This led to the conclusion that critical oocyte reprogramming factors present in the metaphase but not in the interphase cytoplasm are 'trapped' inside the nucleus during interphase and effectively removed during enucleation. Here we investigated the presence of reprogramming activity in the cytoplasm of interphase two-cell mouse embryos (I2C). First, the presence of candidate reprogramming factors was documented in both intact and enucleated metaphase and interphase zygotes and two-cell embryos. Consequently, enucleation did not provide a likely explanation for the inability of interphase cytoplasm to induce reprogramming. Second, when we carefully synchronized the cell cycle stage between the transplanted nucleus (ES cell, fetal fibroblast or terminally differentiated cumulus cell) and the recipient I2C cytoplasm, the reconstructed SCNT embryos developed into blastocysts and ES cells capable of contributing to traditional germline and tetraploid chimaeras. Last, direct transfer of cloned embryos, reconstructed with ES cell nuclei, into recipients resulted in live offspring. Thus, the cytoplasm of I2C supports efficient reprogramming, with cell cycle synchronization between the donor nucleus and recipient cytoplasm as the most critical parameter determining success. The ability to use interphase cytoplasm in SCNT could aid efforts to generate autologous human ES cells for regenerative applications, as donated or discarded embryos are more accessible than unfertilized MII oocytes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4124901/" 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/PMC4124901/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kang, Eunju -- Wu, Guangming -- Ma, Hong -- Li, Ying -- Tippner-Hedges, Rebecca -- Tachibana, Masahito -- Sparman, Michelle -- Wolf, Don P -- Scholer, Hans R -- Mitalipov, Shoukhrat -- P51 OD011092/OD/NIH HHS/ -- P51OD011092/OD/NIH HHS/ -- R01 EY021214/EY/NEI NIH HHS/ -- R01 HD057121/HD/NICHD NIH HHS/ -- R01 HD059946/HD/NICHD NIH HHS/ -- R01 HD063276/HD/NICHD NIH HHS/ -- R01EY021214/EY/NEI NIH HHS/ -- R01HD057121/HD/NICHD NIH HHS/ -- R01HD059946/HD/NICHD NIH HHS/ -- R01HD063276/HD/NICHD NIH HHS/ -- England -- Nature. 2014 May 1;509(7498):101-4. doi: 10.1038/nature13134. Epub 2014 Mar 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon 97006, USA. ; Max Planck Institute for Molecular Biomedicine, Munster 48149, Germany. ; 1] Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon 97006, USA [2] South Miyagi Medical Center, Miyagi 989-1253, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24670652" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Count ; *Cellular Reprogramming ; Cloning, Organism ; Cytoplasm/*metabolism ; Embryo, Mammalian/*cytology ; Embryonic Stem Cells/*cytology ; Female ; Induced Pluripotent Stem Cells/*cytology ; *Interphase ; Male ; Metaphase ; Mice ; *Nuclear Transfer Techniques
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  • 6
    Publication Date: 2014-07-11
    Description: Human pluripotent stem cells hold potential for regenerative medicine, but available cell types have significant limitations. Although embryonic stem cells (ES cells) from in vitro fertilized embryos (IVF ES cells) represent the 'gold standard', they are allogeneic to patients. Autologous induced pluripotent stem cells (iPS cells) are prone to epigenetic and transcriptional aberrations. To determine whether such abnormalities are intrinsic to somatic cell reprogramming or secondary to the reprogramming method, genetically matched sets of human IVF ES cells, iPS cells and nuclear transfer ES cells (NT ES cells) derived by somatic cell nuclear transfer (SCNT) were subjected to genome-wide analyses. Both NT ES cells and iPS cells derived from the same somatic cells contained comparable numbers of de novo copy number variations. In contrast, DNA methylation and transcriptome profiles of NT ES cells corresponded closely to those of IVF ES cells, whereas iPS cells differed and retained residual DNA methylation patterns typical of parental somatic cells. Thus, human somatic cells can be faithfully reprogrammed to pluripotency by SCNT and are therefore ideal for cell replacement therapies.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ma, Hong -- Morey, Robert -- O'Neil, Ryan C -- He, Yupeng -- Daughtry, Brittany -- Schultz, Matthew D -- Hariharan, Manoj -- Nery, Joseph R -- Castanon, Rosa -- Sabatini, Karen -- Thiagarajan, Rathi D -- Tachibana, Masahito -- Kang, Eunju -- Tippner-Hedges, Rebecca -- Ahmed, Riffat -- Gutierrez, Nuria Marti -- Van Dyken, Crystal -- Polat, Alim -- Sugawara, Atsushi -- Sparman, Michelle -- Gokhale, Sumita -- Amato, Paula -- Wolf, Don P -- Ecker, Joseph R -- Laurent, Louise C -- Mitalipov, Shoukhrat -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Jul 10;511(7508):177-83. doi: 10.1038/nature13551. Epub 2014 Jul 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Center for Embryonic Cell and Gene Therapy, Oregon Health & Science University, 3303 Southwest Bond Avenue, Portland, Oregon 97239, USA [2] Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, 505 Northwest 185th Avenue, Beaverton, Oregon 97006, USA [3]. ; 1] Department of Reproductive Medicine, University of California, San Diego, Sanford Consortium for Regenerative Medicine, 2880 Torrey Pines Scenic Drive, La Jolla, California 92037, USA [2]. ; 1] Genomic Analysis Laboratory, the Salk Institute for Biological Studies, La Jolla, California 92037, USA [2] Bioinformatics Program, University of California at San Diego, La Jolla, California 92093, USA. ; 1] Center for Embryonic Cell and Gene Therapy, Oregon Health & Science University, 3303 Southwest Bond Avenue, Portland, Oregon 97239, USA [2] Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, 505 Northwest 185th Avenue, Beaverton, Oregon 97006, USA. ; Genomic Analysis Laboratory, the Salk Institute for Biological Studies, La Jolla, California 92037, USA. ; Department of Reproductive Medicine, University of California, San Diego, Sanford Consortium for Regenerative Medicine, 2880 Torrey Pines Scenic Drive, La Jolla, California 92037, USA. ; 1] Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, 505 Northwest 185th Avenue, Beaverton, Oregon 97006, USA [2] Department of Obstetrics and Gynecology, South Miyagi Medical Center, Shibata-gun, Miyagi 989-1253, Japan (M.T.); Department of Cell and Molecular Biology, Karolinska Institutet, SE-17177 Stockholm, Sweden (A.P.). ; Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, 505 Northwest 185th Avenue, Beaverton, Oregon 97006, USA. ; University Pathologists LLC, Boston University School of Medicine, Roger Williams Medical Center, Providence, Rhode Island 02118, USA. ; Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Oregon Health & Science University, 3181 Southwest Sam Jackson Park Road, Portland, Oregon 97239, USA. ; 1] Genomic Analysis Laboratory, the Salk Institute for Biological Studies, La Jolla, California 92037, USA [2] Howard Hughes Medical Institute, the Salk Institute for Biological Studies, La Jolla, California 92037, USA. ; 1] Center for Embryonic Cell and Gene Therapy, Oregon Health & Science University, 3303 Southwest Bond Avenue, Portland, Oregon 97239, USA [2] Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, 505 Northwest 185th Avenue, Beaverton, Oregon 97006, USA [3] Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Oregon Health & Science University, 3181 Southwest Sam Jackson Park Road, Portland, Oregon 97239, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25008523" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; *Cellular Reprogramming ; Chromosome Aberrations ; Chromosomes, Human, X/genetics/metabolism ; DNA Copy Number Variations ; DNA Methylation ; Genome-Wide Association Study ; Genomic Imprinting ; Humans ; Nuclear Transfer Techniques/standards ; Pluripotent Stem Cells/cytology/*metabolism ; Transcriptome
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  • 7
    Publication Date: 2011-04-12
    Description: Whole-genome duplication (WGD), or polyploidy, followed by gene loss and diploidization has long been recognized as an important evolutionary force in animals, fungi and other organisms, especially plants. The success of angiosperms has been attributed, in part, to innovations associated with gene or whole-genome duplications, but evidence for proposed ancient genome duplications pre-dating the divergence of monocots and eudicots remains equivocal in analyses of conserved gene order. Here we use comprehensive phylogenomic analyses of sequenced plant genomes and more than 12.6 million new expressed-sequence-tag sequences from phylogenetically pivotal lineages to elucidate two groups of ancient gene duplications-one in the common ancestor of extant seed plants and the other in the common ancestor of extant angiosperms. Gene duplication events were intensely concentrated around 319 and 192 million years ago, implicating two WGDs in ancestral lineages shortly before the diversification of extant seed plants and extant angiosperms, respectively. Significantly, these ancestral WGDs resulted in the diversification of regulatory genes important to seed and flower development, suggesting that they were involved in major innovations that ultimately contributed to the rise and eventual dominance of seed plants and angiosperms.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jiao, Yuannian -- Wickett, Norman J -- Ayyampalayam, Saravanaraj -- Chanderbali, Andre S -- Landherr, Lena -- Ralph, Paula E -- Tomsho, Lynn P -- Hu, Yi -- Liang, Haiying -- Soltis, Pamela S -- Soltis, Douglas E -- Clifton, Sandra W -- Schlarbaum, Scott E -- Schuster, Stephan C -- Ma, Hong -- Leebens-Mack, Jim -- dePamphilis, Claude W -- England -- Nature. 2011 May 5;473(7345):97-100. doi: 10.1038/nature09916. Epub 2011 Apr 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Intercollege Graduate Degree Program in Plant Biology, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21478875" target="_blank"〉PubMed〈/a〉
    Keywords: Angiosperms/*classification/*genetics ; *Evolution, Molecular ; Genome, Plant/*genetics ; Genomics ; Phylogeny ; *Polyploidy
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  • 8
    Publication Date: 2016-01-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lin, Han -- Zeng, Saixing -- Ma, Hanyang -- England -- Nature. 2016 Jan 21;529(7586):283. doi: 10.1038/529283e.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Shanghai Jiao Tong University, Shanghai, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26791709" target="_blank"〉PubMed〈/a〉
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  • 9
    Publication Date: 2016-03-17
    Description: The integrated stress response (ISR) is a homeostatic mechanism by which eukaryotic cells sense and respond to stress-inducing signals, such as amino acid starvation. General controlled non-repressed (GCN2) kinase is a key orchestrator of the ISR, and modulates protein synthesis in response to amino acid starvation. Here we demonstrate in mice that GCN2 controls intestinal inflammation by suppressing inflammasome activation. Enhanced activation of ISR was observed in intestinal antigen presenting cells (APCs) and epithelial cells during amino acid starvation, or intestinal inflammation. Genetic deletion of Gcn2 (also known as Eif2ka4) in CD11c(+) APCs or intestinal epithelial cells resulted in enhanced intestinal inflammation and T helper 17 cell (TH17) responses, owing to enhanced inflammasome activation and interleukin (IL)-1beta production. This was caused by reduced autophagy in Gcn2(-/-) intestinal APCs and epithelial cells, leading to increased reactive oxygen species (ROS), a potent activator of inflammasomes. Thus, conditional ablation of Atg5 or Atg7 in intestinal APCs resulted in enhanced ROS and TH17 responses. Furthermore, in vivo blockade of ROS and IL-1beta resulted in inhibition of TH17 responses and reduced inflammation in Gcn2(-/-) mice. Importantly, acute amino acid starvation suppressed intestinal inflammation via a mechanism dependent on GCN2. These results reveal a mechanism that couples amino acid sensing with control of intestinal inflammation via GCN2.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4854628/" 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/PMC4854628/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ravindran, Rajesh -- Loebbermann, Jens -- Nakaya, Helder I -- Khan, Nooruddin -- Ma, Hualing -- Gama, Leonardo -- Machiah, Deepa K -- Lawson, Benton -- Hakimpour, Paul -- Wang, Yi-chong -- Li, Shuzhao -- Sharma, Prachi -- Kaufman, Randal J -- Martinez, Jennifer -- Pulendran, Bali -- R01 DK088227/DK/NIDDK NIH HHS/ -- R01 DK103185/DK/NIDDK NIH HHS/ -- R37 AI048638/AI/NIAID NIH HHS/ -- R37 DK042394/DK/NIDDK NIH HHS/ -- R37 DK057665/DK/NIDDK NIH HHS/ -- U19 AI057266/AI/NIAID NIH HHS/ -- U19 AI090023/AI/NIAID NIH HHS/ -- ZIA ES103286-01/Intramural NIH HHS/ -- England -- Nature. 2016 Mar 24;531(7595):523-7. doi: 10.1038/nature17186. Epub 2016 Mar 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Emory Vaccine Center, Yerkes National Primate Research Center, 954 Gatewood Road, Atlanta, Georgia 30329, USA. ; School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo 05508, Brazil. ; Department of Biotechnology and Bioinformatics, School of Life Sciences, University of Hyderabad, Hyderabad 500 046, India. ; Division of Pathology, Yerkes National Primate Research Center, 954 Gatewood Road, Atlanta, Georgia 30329, USA. ; Virology Core, Emory Vaccine Center and Yerkes National Primate Research Center, 954 Gatewood Road, Atlanta, Georgia 30329, USA. ; Degenerative Disease Program, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, California 92037 USA. ; National Institute of Environmental Health Sciences, Mail Drop D2-01 Research Triangle Park, North Carolina 27709, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26982722" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acids/administration & dosage/deficiency/*metabolism/pharmacology ; Animals ; Antigen-Presenting Cells/immunology/metabolism ; Autophagy ; Colitis/etiology/*metabolism/pathology/prevention & control ; Disease Models, Animal ; Epithelial Cells/metabolism ; Female ; Humans ; Inflammasomes/*antagonists & inhibitors/metabolism ; Inflammation/etiology/*metabolism/pathology/prevention & control ; Interleukin-1beta/immunology ; Intestines/*metabolism/*pathology ; Male ; Mice ; Microtubule-Associated Proteins/deficiency/metabolism ; Protein-Serine-Threonine Kinases/deficiency/genetics/*metabolism ; Reactive Oxygen Species/metabolism ; Stress, Physiological ; Th17 Cells/immunology ; Ubiquitin-Activating Enzymes/deficiency/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 10
    Publication Date: 2015-07-16
    Description: Mitochondria have a major role in energy production via oxidative phosphorylation, which is dependent on the expression of critical genes encoded by mitochondrial (mt)DNA. Mutations in mtDNA can cause fatal or severely debilitating disorders with limited treatment options. Clinical manifestations vary based on mutation type and heteroplasmy (that is, the relative levels of mutant and wild-type mtDNA within each cell). Here we generated genetically corrected pluripotent stem cells (PSCs) from patients with mtDNA disease. Multiple induced pluripotent stem (iPS) cell lines were derived from patients with common heteroplasmic mutations including 3243A〉G, causing mitochondrial encephalomyopathy and stroke-like episodes (MELAS), and 8993T〉G and 13513G〉A, implicated in Leigh syndrome. Isogenic MELAS and Leigh syndrome iPS cell lines were generated containing exclusively wild-type or mutant mtDNA through spontaneous segregation of heteroplasmic mtDNA in proliferating fibroblasts. Furthermore, somatic cell nuclear transfer (SCNT) enabled replacement of mutant mtDNA from homoplasmic 8993T〉G fibroblasts to generate corrected Leigh-NT1 PSCs. Although Leigh-NT1 PSCs contained donor oocyte wild-type mtDNA (human haplotype D4a) that differed from Leigh syndrome patient haplotype (F1a) at a total of 47 nucleotide sites, Leigh-NT1 cells displayed transcriptomic profiles similar to those in embryo-derived PSCs carrying wild-type mtDNA, indicative of normal nuclear-to-mitochondrial interactions. Moreover, genetically rescued patient PSCs displayed normal metabolic function compared to impaired oxygen consumption and ATP production observed in mutant cells. We conclude that both reprogramming approaches offer complementary strategies for derivation of PSCs containing exclusively wild-type mtDNA, through spontaneous segregation of heteroplasmic mtDNA in individual iPS cell lines or mitochondrial replacement by SCNT in homoplasmic mtDNA-based disease.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ma, Hong -- Folmes, Clifford D L -- Wu, Jun -- Morey, Robert -- Mora-Castilla, Sergio -- Ocampo, Alejandro -- Ma, Li -- Poulton, Joanna -- Wang, Xinjian -- Ahmed, Riffat -- Kang, Eunju -- Lee, Yeonmi -- Hayama, Tomonari -- Li, Ying -- Van Dyken, Crystal -- Gutierrez, Nuria Marti -- Tippner-Hedges, Rebecca -- Koski, Amy -- Mitalipov, Nargiz -- Amato, Paula -- Wolf, Don P -- Huang, Taosheng -- Terzic, Andre -- Laurent, Louise C -- Izpisua Belmonte, Juan Carlos -- Mitalipov, Shoukhrat -- England -- Nature. 2015 Aug 13;524(7564):234-8. doi: 10.1038/nature14546. Epub 2015 Jul 15.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Center for Embryonic Cell and Gene Therapy, Oregon Health &Science University, 3303 S.W. Bond Avenue, Portland, Oregon 97239, USA [2] Division of Reproductive &Developmental Sciences, Oregon National Primate Research Center, Oregon Health &Science University, 505 N.W. 185th Avenue, Beaverton, Oregon 97006, USA. ; Center for Regenerative Medicine and Department of Medicine, Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota 55905, USA. ; Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA. ; Department of Reproductive Medicine, University of California, San Diego, Sanford Consortium for Regenerative Medicine, 2880 Torrey Pines Scenic Drive, La Jolla, California 92037, USA. ; Department of Obstetrics and Gynaecology, John Radcliffe Hospital, University of Oxford, Headington, Oxford OX3 9DU, UK. ; Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA. ; Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Oregon Health and Science University, 3181 Southwest Sam Jackson Park Road, Portland, Oregon 97239, USA. ; Division of Reproductive &Developmental Sciences, Oregon National Primate Research Center, Oregon Health &Science University, 505 N.W. 185th Avenue, Beaverton, Oregon 97006, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26176921" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/metabolism ; Animals ; Cell Line ; DNA, Mitochondrial/*genetics ; Embryo, Mammalian/cytology ; Fibroblasts/cytology/metabolism/pathology ; Gene Expression Profiling ; Haplotypes/genetics ; Humans ; Induced Pluripotent Stem Cells/*metabolism ; Leigh Disease/genetics/metabolism/pathology ; Mice ; Mitochondria/*genetics/*metabolism/pathology ; Mitochondrial Diseases/*genetics/*metabolism/pathology ; Mitochondrial Encephalomyopathies/genetics/metabolism/pathology ; Mutation/genetics ; Nuclear Transfer Techniques ; Nucleotides/genetics ; Oxygen Consumption ; Polymorphism, Single Nucleotide/genetics ; Sequence Analysis, RNA ; Skin/cytology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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