Two paternal genomes are compatible with dopaminergic in vitro and in vivo differentiation

Choi, Soon Won; Eckardt, Sigrid; Ahmad, Ruhel; Wolber, Wanja; McLaughlin, K. John; Sirén, Anna‐Leena; Müller, Albrecht

doi:10.1387/ijdb.103188sc

Cited by 4 publications

(3 citation statements)

References 59 publications

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“…We further show that PG neuron-like cells were capable to generate action potentials and possessed membrane characteristics similar to newly formed neurons [26], [35]. The unperturbed neural differentiation potential of hpESCs is consistent with earlier reports of successful murine AG ESC-derived neurogenesis [11], [12], [16]. Our analyses indicate that uniparental ESCs are less restricted in their neural developmental potential than predicted from in vivo studies [18], [38].…”

Section: Discussionsupporting

confidence: 89%

“…Despite this developmental limitation, stable ESC lines can be isolated from uniparental blastocysts of several species including human [7]–[10]. The in vitro differentiation capacity of murine uniparental ESC into various cell lineages, including neural and transplantable hematopoietic progenitors [11]–[16] indicates that these cells represent a unique model system to study the role of maternal and paternal genomes in normal development and the contribution of imprinting in disease development.…”

Section: Introductionmentioning

confidence: 99%

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Functional Neuronal Cells Generated by Human Parthenogenetic Stem Cells

et al. 2012

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Parent of origin imprints on the genome have been implicated in the regulation of neural cell type differentiation. The ability of human parthenogenetic (PG) embryonic stem cells (hpESCs) to undergo neural lineage and cell type-specific differentiation is undefined. We determined the potential of hpESCs to differentiate into various neural subtypes. Concurrently, we examined DNA methylation and expression status of imprinted genes. Under culture conditions promoting neural differentiation, hpESC-derived neural stem cells (hpNSCs) gave rise to glia and neuron-like cells that expressed subtype-specific markers and generated action potentials. Analysis of imprinting in hpESCs and in hpNSCs revealed that maternal-specific gene expression patterns and imprinting marks were generally maintained in PG cells upon differentiation. Our results demonstrate that despite the lack of a paternal genome, hpESCs generate proliferating NSCs that are capable of differentiation into physiologically functional neuron-like cells and maintain allele-specific expression of imprinted genes. Thus, hpESCs can serve as a model to study the role of maternal and paternal genomes in neural development and to better understand imprinting-associated brain diseases.

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Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Functional Neuronal Cells Generated by Human Parthenogenetic Stem Cells

et al. 2012

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“…These experiments suggested that both parental genomes play nonredundant roles during brain development. However, uniparental murine and human ESCs resemble biparental ("normal") ESCs (N ESCs) in their capacity to proliferate and undergo multilineage in vitro differentiation with similar functional neurogenesis and in vivo neural engraftment (1,(11)(12)(13)(14).…”

Section: Introductionmentioning

confidence: 99%

Human Parthenogenetic Embryonic Stem Cell-Derived Neural Stem Cells Express HLA-G and Show Unique Resistance to NK Cell-Mediated Killing

Schmitt

Eckardt

Schlegel

et al. 2015

Mol Med

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Parent-of-origin imprints have been implicated in the regulation of neural differentiation and brain development. Previously we have shown that, despite the lack of a paternal genome, human parthenogenetic (PG) embryonic stem cells (hESCs) can form proliferating neural stem cells (NSCs) that are capable of differentiation into physiologically functional neurons while maintaining allele-specific expression of imprinted genes. Since biparental ("normal") hESC-derived NSCs (N NSCs) are targeted by immune cells, we characterized the immunogenicity of PG NSCs. Flow cytometry and immunocytochemistry revealed that both N NSCs and PG NSCs exhibited surface expression of human leukocyte antigen (HLA) class I but not HLA-DR molecules. Functional analyses using an in vitro mixed lymphocyte reaction assay resulted in less proliferation of peripheral blood mononuclear cells (PBMC) with PG compared with N NSCs. In addition, natural killer (NK) cells cytolyzed PG less than N NSCs. At a molecular level, expression analyses of immune regulatory factors revealed higher HLA-G levels in PG compared with N NSCs. In line with this finding, MIR152, which represses HLA-G expression, is less transcribed in PG compared with N cells. Blockage of HLA-G receptors ILT2 and KIR2DL4 on natural killer cell leukemia (NKL) cells increased cytolysis of PG NSCs. Together this indicates that PG NSCs have unique immunological properties due to elevated HLA-G expression.

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Effects of Histone Deacetylase Inhibitors on the Early Development of Bovine Androgenetic Embryos

ZhangHualin

XiaoYao

WangXiaomin

et al. 2014

Cellular Reprogramming

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Histone acetylation is one of the most important posttranslational modifications that contribute to transcriptional initiation and chromatin remodeling. In our previous study, we enhanced sperm chromatin remodeling within the bovine sperm injection-derived androgenentic (SpI-AG) embryos by sperm pretreatment, and thereby improved their early developmental competence. In this study, we found that blastocyst development of SpI-AG embryos could be elevated by the histone deacetylase inhibitor (HDACi). First, we optimized the efficacy of two histone deacetylase inhibitors [trichostatin A (TSA) and Scriptaid (SCR)] in a dose (0, 5, 10, 20, 50, and 100 nM for TSA; 0, 50, 100, 200, 300, and 500 nM for SCR, respectively) and time-dependent (0, 10, 15, 20, and 25 h) manner on the developmental capacity of these embryos. Furthermore, we quantitatively assessed the alterations in histone H3 and H4 overall acetylation levels and blastocyst quality of SpI-AG embryos by immunofluorescence staining. We found a significantly improved morula and blastocyst development rate of SpI-AG embryos at a mild dose of TSA (20 nM) or SCR (200 nM) for 15 h after embryo activation. Furthermore, both HDACi noticeably increased the levels of acetylated histone H3 and H4 in SpI-AG blastocyst embryos, whereas, SCR treatment improved the quality of blastocysts when compared with control group. In conclusion, HDACi is beneficial for early development of bovine SpI-AG embryos and can be used to improve the efficiency of its in vitro production.

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Two paternal genomes are compatible with dopaminergic in vitro and in vivo differentiation

Cited by 4 publications

References 59 publications

Functional Neuronal Cells Generated by Human Parthenogenetic Stem Cells

Functional Neuronal Cells Generated by Human Parthenogenetic Stem Cells

Human Parthenogenetic Embryonic Stem Cell-Derived Neural Stem Cells Express HLA-G and Show Unique Resistance to NK Cell-Mediated Killing

Effects of Histone Deacetylase Inhibitors on the Early Development of Bovine Androgenetic Embryos

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