Formation of germ-line chimaeras from embryo-derived teratocarcinoma cell lines

Bradley, Allan; Evans, Martin; Kaufman, M. H.; Robertson, Elizabeth J.

doi:10.1038/309255a0

Cited by 1,377 publications

(688 citation statements)

References 17 publications

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“…Several studies comparing naïve and primed pluripotent stem cells have indicated that the two types of cells exhibit different molecular and functional properties, including colony morphologies, single-cell passage abilities [7,8], dependent signaling pathways [6,9,10], pluripotent gene expression profiles, and, most important, mouse embryo integration capacity to generate cross-species chimeras [7,11,12]. Previous studies have also suggested that human primed iPSCs and mouse EpiSCs can be converted to the naïve ground state via chemical manipulation or the overexpression of specific transcription factors [12][13][14][15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Naïve Induced Pluripotent Stem Cells Generated From β-Thalassemia Fibroblasts Allow Efficient Gene Correction With CRISPR/Cas9

Yang

Zhang

et al. 2015

Stem Cells Translational Medicine

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Conventional primed human embryonic stem cells and induced pluripotent stem cells (iPSCs) exhibit molecular and biological characteristics distinct from pluripotent stem cells in the naïve state. Although naïve pluripotent stem cells show much higher levels of self-renewal ability and multidifferentiation capacity, it is unknown whether naïve iPSCs can be generated directly from patient somatic cells and will be superior to primed iPSCs. In the present study, we used an established 5i/L/FA system to directly reprogram fibroblasts of a patient with b-thalassemia into transgene-free naïve iPSCs with molecular signatures of ground-state pluripotency. Furthermore, these naïve iPSCs can efficiently produce cross-species chimeras. Importantly, using the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 nuclease genome editing system, these naïve iPSCs exhibit significantly improved gene-correction efficiencies compared with the corresponding primed iPSCs. Furthermore, human naïve iPSCs could be directly generated from noninvasively collected urinary cells, which are easily acquired and thus represent an excellent cell resource for further clinical trials. Therefore, our findings demonstrate the feasibility and superiority of using patient-specific iPSCs in the naïve state for disease modeling, gene editing, and future clinical therapy. STEM CELLS TRANSLATIONAL MEDICINE 2016;5:8-19 SIGNIFICANCEIn the present study, transgene-free naïve induced pluripotent stem cells (iPSCs) directly converted from the fibroblasts of a patient with b-thalassemia in a defined culture system were generated. These naïve iPSCs, which show ground-state pluripotency, exhibited significantly improved singlecell cloning ability, recovery capacity, and gene-targeting efficiency compared with conventional primed iPSCs. These results provide an improved strategy for personalized treatment of genetic diseases such as b-thalassemia.

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Section: Introductionmentioning

confidence: 99%

Naïve Induced Pluripotent Stem Cells Generated From β-Thalassemia Fibroblasts Allow Efficient Gene Correction With CRISPR/Cas9

Yang

Zhang

et al. 2015

Stem Cells Translational Medicine

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“…One aspect in this long multistep process that has not been streamlined with regard to the logistics and ethics of mouse breeding is the efficiency or rate of germline transmission (GLT): the transmission of the ES cell‐derived genome through the germline of male chimeras to their offspring (Bradley et al ., 1984). Such chimeras are referred to as germline chimeras.…”

Section: Introductionmentioning

confidence: 99%

Exclusive transmission of the embryonic stem cell‐derived genome through the mouse germline

Köentgen¹,

Lin

Κατίδου

et al. 2016

Genesis

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SummaryGene targeting in embryonic stem (ES) cells remains best practice for introducing complex mutations into the mouse germline. One aspect in this multistep process that has not been streamlined with regard to the logistics and ethics of mouse breeding is the efficiency of germline transmission: the transmission of the ES cell‐derived genome through the germline of chimeras to their offspring. A method whereby male chimeras transmit exclusively the genome of the injected ES cells to their offspring has been developed. The new technology, referred to as goGermline, entails injecting ES cells into blastocysts produced by superovulated homozygous Tsc22d3 floxed females mated with homozygous ROSA26‐Cre males. This cross produces males that are sterile due to a complete cell‐autonomous defect in spermatogenesis. The resulting male chimeras can be sterile but when fertile, they transmit the ES cell‐derived genome to 100% of their offspring. The method was validated extensively and in two laboratories for gene‐targeted ES clones that were derived from the commonly used parental ES cell lines Bruce4, E14, and JM8A3. The complete elimination of the collateral birth of undesired, non‐ES cell‐derived offspring in goGermline technology fulfills the reduction imperative of the 3R principle of humane experimental technique with animals. genesis 54:326–333, 2016. © 2016 The Authors. Genesis Published by Wiley Periodicals, Inc.

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“…Owing to the development of mouse embryonic stem (ES) cells 1,2 and a variety of mutagenic technologies [3][4][5][6][7][8][9][10][11][12] , it is now possible to plan a systematic assault on the mouse genome to document function. The most straightforward way to start this program is to create and characterize null alleles in the germ line.…”

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confidence: 99%

The European dimension for the mouse genome mutagenesis program

et al. 2004

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The European Mouse Mutagenesis Consortium is the European initiative contributing to the international effort on functional annotation of the mouse genome. Its objectives are to establish and integrate mutagenesis platforms, gene expression resources, phenotyping units, storage and distribution centers and bioinformatics resources. The combined efforts will accelerate our understanding of gene function and of human health and disease.

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Formation of germ-line chimaeras from embryo-derived teratocarcinoma cell lines

Cited by 1,377 publications

References 17 publications

Naïve Induced Pluripotent Stem Cells Generated From β-Thalassemia Fibroblasts Allow Efficient Gene Correction With CRISPR/Cas9

Naïve Induced Pluripotent Stem Cells Generated From β-Thalassemia Fibroblasts Allow Efficient Gene Correction With CRISPR/Cas9

Exclusive transmission of the embryonic stem cell‐derived genome through the mouse germline

The European dimension for the mouse genome mutagenesis program

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