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.
View Publication
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.
View Publication
B. S. Souza et al. (dec 2016)
Scientific Reports 6 1 39775
Zika virus infection induces mitosis abnormalities and apoptotic cell death of human neural progenitor cells
Zika virus (ZIKV) infection has been associated with severe complications both in the developing and adult nervous system. To investigate the deleterious effects of ZIKV infection,we used human neural progenitor cells (NPC),derived from induced pluripotent stem cells (iPSC). We found that NPC are highly susceptible to ZIKV and the infection results in cell death. ZIKV infection led to a marked reduction in cell proliferation,ultrastructural alterations and induction of autophagy. Induction of apoptosis of Sox2 + cells was demonstrated by activation of caspases 3/7,8 and 9,and by ultrastructural and flow cytometry analyses. ZIKV-induced death of Sox2 + cells was prevented by incubation with the pan-caspase inhibitor,Z-VAD-FMK. By confocal microscopy analysis we found an increased number of cells with supernumerary centrosomes. Live imaging showed a significant increase in mitosis abnormalities,including multipolar spindle,chromosome laggards,micronuclei and death of progeny after cell division. FISH analysis for chromosomes 12 and 17 showed increased frequency of aneuploidy,such as monosomy,trisomy and polyploidy. Our study reinforces the link between ZIKV and abnormalities in the developing human brain,including microcephaly.
View Publication
EasySep™小鼠TIL（CD45）正选试剂盒
科学海报A Novel mRNA-LNP Platform to Rapidly Generate Functional Forebrain Neurons from hPSCs Using NGN2
实验方案Large-Scale Expansion of hPSCs in 2D Monolayer Culture using mTeSR™ Plus
沪公网安备31010102008431号