Haploid animal cells

Wutz, Anton

doi:10.1242/dev.102202

Cited by 26 publications

(27 citation statements)

References 38 publications

(57 reference statements)

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“…A mutated phenotype is exposed immediately because there is only one copy of a gene on the haploid chromosomes. The use of these cells represents a powerful new technique to interrogate the phenotypic effects of genetic perturbations in human cancer cells, which is not possible with the use of diploid cells [17]. To examine the impact of specific loss of BAP1, BAP1 was knocked out in HAP1 cells using CRISPR/CAS9 (Additional file 2: Table S4).…”

Section: Resultsmentioning

confidence: 99%

BAP1 dependent expression of long non-coding RNA NEAT-1 contributes to sensitivity to gemcitabine in cholangiocarcinoma

et al. 2017

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BackgroundGenetic alterations in chromatin modulators such as BRCA-1 associated protein-1 (BAP1) are the most frequent genetic alteration in intrahepatic cholangiocarcinomas (CCA). We evaluated the contribution of BAP1 expression on tumor cell behavior and therapeutic sensitivity to identify rationale therapeutic strategies.MethodsThe impact of BAP1 expression on sensitivity to therapeutic agents was evaluated in CCA cells with a 7-fold difference in BAP1 expression (KMBC-low, HuCCT1-high) and genetically engineered haplo-insufficient BAP1 knockout cells. We also identified long non-coding RNA genes associated with loss of BAP1 and their role in therapeutic sensitivity.ResultsSensitivity to gemcitabine was greater in low BAP1 expressing or BAP1 knockout cells compared with the high BAP1 expressing cells or control haplo-insufficient cells respectively. Similar results were observed with TSA, olaparib, b-AP15 but not with GSK126. A differential synergistic effect was observed in combinations of gemcitabine with olaparib or GSK126 in KMBC cells and TSA or bAP15 in HuCCT1 cells, indicating BAP1 dependent target-specific synergism and sensitivity to gemcitabine. A BAP1 dependent alteration in expression of lncRNA NEAT-1 was identified by RT-PCR based lncRNA expression profiling, and an inverse relationship between this lncRNA and BAP1 was observed in analysis of the Tumor Cancer Genome Atlas cholangiocarcinoma dataset. Exogenous modulation of NEAT-1 and/or BAP1 expression altered tumor cell phenotype and modulated sensitivity to gemcitabine.ConclusionsNEAT-1 is a downstream effector of gemcitabine sensitivity in CCA. The expression of BAP1 is a determinant of sensitivity to therapeutic drugs that can be exploited to enhance responses through combination strategies.Electronic supplementary materialThe online version of this article (doi:10.1186/s12943-017-0587-x) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

BAP1 dependent expression of long non-coding RNA NEAT-1 contributes to sensitivity to gemcitabine in cholangiocarcinoma

et al. 2017

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“…Haploid embryonic stem cells (hESCs) are a group of cells containing only one set of chromosome and resembling characteristic with normal embryonic stem cells (ESCs), and giving rise to a wide range of functioning cell of all tissues and organs [1]. Since 2011, several research groups have independently established haploid embryonic stem cells (hESCs) successfully from mouse haploid parthenogenetic or androgenetic embryos [2,3].…”

Section: Introductionmentioning

confidence: 99%

SIRT1 regulates autophagy and diploidization in parthenogenetic haploid embryonic stem cells

Zhao

Yang

Cui

2015

Biochemical and Biophysical Research Communications

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“…In this regard, the generation of precisely defined cell lines with gene modification may be helpful, though only feasible through a concerted effort of a large consortium. There is considerable development in the creation of mammalian haploid cell lines that will overcome some limitations of this technology due to mixed genetic alterations in di--or poly--ploid cell lines 76 .…”

Section: Interactome Profiling: Ppi--approachesmentioning

confidence: 99%

Application guide for omics approaches to cell signaling

et al. 2015

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Research in signal transduction aims to identify the functions of different signaling pathways in physiological and pathological states. Traditional techniques using biochemical, genetic or cell biological approaches have made important contributions to our understanding of cellular signaling. However, the single--gene approach does not take into account the whole complexity of cell signaling. With the availability of OMICs--techniques, great progress has been made in understanding signaling networks. OMICs approaches can be classified into two categories: "molecular profiling", including genomic--, proteomic--, post--translational modification--and interactome--profiling; and "molecular perturbation", including genetic and functional perturbations.Due to the ever--growing field of method development to characterize cellular processes on genomic and proteomic levels and in many other dimensions, it has become a challenge to select and apply the appropriate methods suitable for addressing a specific biological question. In this perspective, we will describe some selected OMICs--techniques and discuss their applicability to cell signaling research.3

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Haploid animal cells

Cited by 26 publications

References 38 publications

BAP1 dependent expression of long non-coding RNA NEAT-1 contributes to sensitivity to gemcitabine in cholangiocarcinoma

BAP1 dependent expression of long non-coding RNA NEAT-1 contributes to sensitivity to gemcitabine in cholangiocarcinoma

SIRT1 regulates autophagy and diploidization in parthenogenetic haploid embryonic stem cells

Application guide for omics approaches to cell signaling

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