Derivation of a diploid human embryonic stem cell line from a mononuclear zygote

Suss-Toby, Edith

doi:10.1093/humrep/deh135

Cited by 78 publications

(44 citation statements)

References 13 publications

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“…Resultant diploid embryos were previously confirmed to undergo predominantly normal fertilization owing to the asynchronous formation of two pronuclei [19,21], and a normal diploid hESC line has been derived from these oocytes [28]. These results coincide with our unpublished data, which show that, out of 16 hESC lines that are derived from one-pronuclear oocytes, the majority were of biparental origin.…”

Section: Discussionsupporting

confidence: 87%

A highly homozygous and parthenogenetic human embryonic stem cell line derived from a one-pronuclear oocyte following in vitro fertilization procedure

et al. 2007

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Homozygous human embryonic stem cells (hESCs) are thought to be better cell sources for hESC banking because their human leukocyte antigen (HLA) haplotype would strongly increase the degree of matching for certain populations with relatively smaller cohorts of cell lines. Homozygous hESCs can be generated from parthenogenetic embryos, but only heterozygous hESCs have been established using the current strategy to artificially activate the oocyte without second polar body extrusion. Here we report the first successful derivation of a human homozygous ESC line (chHES-32) from a one-pronuclear oocyte following routine in vitro fertilization treatment. chHES-32 cells express common markers and genes with normal hESCs. They have been propagated in an undifferentiated state for more than a year (>P50) and have maintained a stable karyotype of 46, XX. When differentiated in vivo and in vitro, chHES-32 cells can form derivatives from all three embryonic germ layers. The almost undetectable expression of five paternally expressed imprinted genes and their HLA genotype identical to the oocyte donor indicated their parthenogenetic origin. Using genome-wide single-nucleotide polymorphism analysis and DNA fingerprinting, the homozygosity of chHES-32 cells was further confirmed. The results indicated that 'unwanted' one-pronuclear oocytes might be a potential source for human homozygous and parthenogenetic ESCs, and suggested an alternative strategy for obtaining homozygous hESC lines from parthenogenetic haploid oocytes.

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Section: Discussionsupporting

confidence: 87%

A highly homozygous and parthenogenetic human embryonic stem cell line derived from a one-pronuclear oocyte following in vitro fertilization procedure

et al. 2007

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“…Human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) derived from embryos or via somatic cell reprogramming [1][2][3][4], respectively, represent a primed state of pluripotency similar to mouse epiblast stem cells (EpiSCs) [5,6] but distinct from the naïve pluripotent state of mouse ESCs and iPSCs [7]. 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].…”

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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“…These data are very encouraging since human IVF embryos have revealed an unexpectedly high incidence of postzygotic chromosomal abnormalities which reduce the quality of recovered embryos and contribute to early pregnancy loss after embryo transfer (Delhanty & Handyside 1995, Trounson & Bongso 1996, Handyside & Delhanty 1997, Munne 2002. Surprisingly, it has been demonstrated that even aneuploid zygotes can be used as a source for derivation of hES cells (Suss-Toby et al 2004) that could be used for research purposes.…”

Section: What Is Important For the Derivation Of Hes Cells?mentioning

confidence: 93%

Derivation, growth and applications of human embryonic stem cells

Stojković¹,

Lako²,

Strachan³

et al. 2004

Reproduction

127

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Human embryonic stem (hES) cells are pluripotent cells derived from the inner cell mass cells of blastocysts with the potential to maintain an undifferentiated state indefinitely. Fully characterised hES cell lines express typical stem cell markers, possess high levels of telomerase activity, show normal karyotype and have the potential to differentiate into numerous cell types under in vitro and in vivo conditions. Therefore, hES cells are potentially valuable for the development of cell transplantation therapies for the treatment of various human diseases. However, there are a number of factors which may limit the medical application of hES cells: (a) continuous culture of hES cells in an undifferentiated state requires the presence of feeder layers and animal-based ingredients which incurs a risk of cross-transfer of pathogens; (b) hES cells demonstrate high genomic instability and non-predictable differentiation after long-term growth; and (c) differentiated hES cells express molecules which could cause immune rejection. In this review we summarise recent progress in the derivation and growth of undifferentiated hES cells and their differentiated progeny, and the problems associated with these techniques. We also examine the potential use of the therapeutic cloning technique to derive isogenic hES cells.

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Derivation of a diploid human embryonic stem cell line from a mononuclear zygote

Cited by 78 publications

References 13 publications

A highly homozygous and parthenogenetic human embryonic stem cell line derived from a one-pronuclear oocyte following in vitro fertilization procedure

A highly homozygous and parthenogenetic human embryonic stem cell line derived from a one-pronuclear oocyte following in vitro fertilization procedure

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

Derivation, growth and applications of human embryonic stem cells

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