Tagliafierro L et al. (NOV 2017)
Alzheimer's & dementia : the journal of the Alzheimer's Association 13 11 1237--1250
Genetic analysis of α-synuclein 3' untranslated region and its corresponding microRNAs in relation to Parkinson's disease compared to dementia with Lewy bodies.
INTRODUCTION The α-synuclein (SNCA) gene has been implicated in the etiology of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). METHODS A computational analysis of SNCA 3' untranslated region to identify potential microRNA (miRNA) binding sites and quantitative real-time polymerase chain reaction (PCR) to determine their expression in isogenic induced pluripotent stem cell-derived dopaminergic and cholinergic neurons as a model of PD and DLB,respectively,were performed. In addition,we performed a deep sequencing analysis of the SNCA 3' untranslated region of autopsy-confirmed cases of PD,DLB,and normal controls,followed by genetic association analysis of the identified variants. RESULTS We identified four miRNA binding sites and observed a neuronal-type-specific expression profile for each miRNA in the different isogenic induced pluripotent stem cell-derived dopaminergic and cholinergic neurons. Furthermore,we found that the short structural variant rs777296100-polyT was moderately associated with DLB but not with PD. DISCUSSION We suggest that the regulation of SNCA expression through miRNAs is neuronal-type-specific and possibly plays a part in the phenotypic heterogeneity of synucleinopathies. Furthermore,genetic variability in the SNCA gene may contribute to synucleinopathies in a pathology-specific manner.
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产品号#:
05790
05792
05793
05794
05795
产品名:
BrainPhys™神经元培养基
BrainPhys™神经元培养基和SM1试剂盒
BrainPhys™ 神经元培养基N2-A和SM1试剂盒
BrainPhys™原代神经元试剂盒
BrainPhys™ hPSC 神经元试剂盒
Werner A et al. (SEP 2015)
Nature 525 7570 523--527
Cell-fate determination by ubiquitin-dependent regulation of translation
Metazoan development depends on the accurate execution of differentiation programs that allow pluripotent stem cells to adopt specific fates. Differentiation requires changes to chromatin architecture and transcriptional networks,yet whether other regulatory events support cell-fate determination is less well understood. Here we identify the ubiquitin ligase CUL3 in complex with its vertebrate-specific substrate adaptor KBTBD8 (CUL3(KBTBD8)) as an essential regulator of human and Xenopus tropicalis neural crest specification. CUL3(KBTBD8) monoubiquitylates NOLC1 and its paralogue TCOF1,the mutation of which underlies the neurocristopathy Treacher Collins syndrome. Ubiquitylation drives formation of a TCOF1-NOLC1 platform that connects RNA polymerase I with ribosome modification enzymes and remodels the translational program of differentiating cells in favour of neural crest specification. We conclude that ubiquitin-dependent regulation of translation is an important feature of cell-fate determination.
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产品号#:
05872
05873
07920
07922
05210
05215
34811
34815
34850
34821
34825
34860
05835
05839
100-0483
100-0484
产品名:
ACCUTASE™
ACCUTASE™
AggreWell™ 800 24孔板,1个
AggreWell™ 800 24孔板,5个
AggreWell™ 800 24孔板启动套装
AggreWell™ 800 6孔板,1个
AggreWell™ 800 6孔板,5个
AggreWell™ 800 6孔板启动套装
STEMdiff™ 神经诱导培养基
STEMdiff™ 神经诱导培养基
Hausser Scientificᵀᴹ 明线血球计数板
ReLeSR™
Belle K et al. (JAN 2017)
Neuroscience letters 637 201--206
Generation of disease-specific autopsy-confirmed iPSCs lines from postmortem isolated Peripheral Blood Mononuclear Cells
Understanding the molecular mechanisms that underlie neurodegenerative disorders has been hampered by a lack of readily available model systems that replicate the complexity of the human disease. Recent advances in stem cell technology have facilitated the derivation of patient-specific stem cells from a variety of differentiated cell types. These induced pluripotent stem cells (iPSCs) are attractive disease models since they can be grown and differentiated to produce large numbers of disease-relevant cell types. However,most iPSC lines are derived in advance of,and without the benefit of,neuropathological confirmation of the donor - the gold standard for many disease classifications and measurement of disease severity. While others have reported the generation of autopsy-confirmed iPSC lines from patient explants,these methods require outgrowth of cadaver tissue,which require additional time and is often only successul 50% of the time. Here we report the rapid generation of autopsy-confirmed iPSC lines from peripheral blood mononuclear cells (PBMCs) drawn postmortem. Since this approach doesn't require the propagation of previously frozen cadaver tissue,iPSC can be rapidly and efficiently produced from patients with autopsy-confirmed pathology. These matched iPSC-derived patient-specific neurons and postmortem brain tissue will support studies of specific mechanisms that drive the pathogenesis of neurodegenerative diseases.
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