Zhu X et al. (JUL 2010)
Molecular cancer therapeutics 9 7 2131--41
Identification of internalizing human single-chain antibodies targeting brain tumor sphere cells.
Glioblastoma multiforme (GBM) is the most common and aggressive form of primary brain tumor for which there is no curative treatment to date. Resistance to conventional therapies and tumor recurrence pose major challenges to treatment and management of this disease,and therefore new therapeutic strategies need to be developed. Previous studies by other investigators have shown that a subpopulation of GBM cells can grow as neurosphere-like cells when cultured in restrictive medium and exhibits enhanced tumor-initiating ability and resistance to therapy. We report here the identification of internalizing human single-chain antibodies (scFv) targeting GBM tumor sphere cells. We selected a large naive phage antibody display library on the glycosylation-dependent CD133 epitope-positive subpopulation of GBM cells grown as tumor spheres and identified internalizing scFvs that target tumor sphere cells broadly,as well as scFvs that target the CD133-positive subpopulation. These scFvs were found to be efficiently internalized by GBM tumor sphere cells. One scFv GC4 inhibited self-renewal of GBM tumor sphere cells in vitro. We have further developed a full-length human IgG1 based on this scFv,and found that it potently inhibits proliferation of GBM tumor sphere cells and GBM cells grown in regular nonselective medium. Taken together,these results show that internalizing human scFvs targeting brain tumor sphere cells can be readily identified from a phage antibody display library,which could be useful for further development of novel therapies that target subpopulations of GBM cells to combat recurrence and resistance to treatment.
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产品类型：
产品号#：
05751
产品名：
NeuroCult™ NS-A 扩增试剂盒（人）
Vukovic J et al. (APR 2013)
Journal of Neuroscience 33 15 6603--6613
Immature Doublecortin-Positive Hippocampal Neurons Are Important for Learning But Not for Remembering
It is now widely accepted that hippocampal neurogenesis underpins critical cognitive functions,such as learning and memory. To assess the behavioral importance of adult-born neurons,we developed a novel knock-in mouse model that allowed us to specifically and reversibly ablate hippocampal neurons at an immature stage. In these mice,the diphtheria toxin receptor (DTR) is expressed under control of the doublecortin (DCX) promoter,which allows for specific ablation of immature DCX-expressing neurons after administration of diphtheria toxin while leaving the neural precursor pool intact. Using a spatially challenging behavioral test (a modified version of the active place avoidance test),we present direct evidence that immature DCX-expressing neurons are required for successful acquisition of spatial learning,as well as reversal learning,but are not necessary for the retrieval of stored long-term memories. Importantly,the observed learning deficits were rescued as newly generated immature neurons repopulated the granule cell layer upon termination of the toxin treatment. Repeat (or cyclic) depletion of immature neurons reinstated behavioral deficits if the mice were challenged with a novel task. Together,these findings highlight the potential of stimulating neurogenesis as a means to enhance learning.
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Badizadegan K et al. (NOV 2014)
AJP: Gastrointestinal and Liver Physiology 307 10 G1002--G1012
Presence of intramucosal neuroglial cells in normal and aganglionic human colon
The enteric nervous system (ENS) is composed of neural crest-derived neurons (also known as ganglion cells) the cell bodies of which are located in the submucosal and myenteric plexuses of the intestinal wall. Intramucosal ganglion cells are known to exist but are rare and often considered ectopic. Also derived from the neural crest are enteric glial cells that populate the ganglia and the associated nerves,as well as the lamina propria of the intestinal mucosa. In Hirschsprung disease (HSCR),ganglion cells are absent from the distal gut because of a failure of neural crest-derived progenitor cells to complete their rostrocaudal migration during embryogenesis. The fate of intramucosal glial cells in human HSCR is essentially unknown. We demonstrate a network of intramucosal cells that exhibit dendritic morphology typical of neurons and glial cells. These dendritic cells are present throughout the human gut and express Tuj1,S100,glial fibrillary acidic protein,CD56,synaptophysin,and calretinin,consistent with mixed or overlapping neuroglial differentiation. The cells are present in aganglionic colon from patients with HSCR,but with an altered immunophenotype. Coexpression of Tuj1 and HNK1 in this cell population supports a neural crest origin. These findings extend and challenge the current understanding of ENS microanatomy and suggest the existence of an intramucosal population of neural crest-derived cells,present in HSCR,with overlapping immunophenotype of neurons and glia. Intramucosal neuroglial cells have not been previously recognized,and their presence in HSCR poses new questions about ENS development and the pathobiology of HSCR that merit further investigation.
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Piccirillo SGM et al. (DEC 2006)
Nature 444 7120 761--5
Bone morphogenetic proteins inhibit the tumorigenic potential of human brain tumour-initiating cells.
Transformed,oncogenic precursors,possessing both defining neural-stem-cell properties and the ability to initiate intracerebral tumours,have been identified in human brain cancers. Here we report that bone morphogenetic proteins (BMPs),amongst which BMP4 elicits the strongest effect,trigger a significant reduction in the stem-like,tumour-initiating precursors of human glioblastomas (GBMs). Transient in vitro exposure to BMP4 abolishes the capacity of transplanted GBM cells to establish intracerebral GBMs. Most importantly,in vivo delivery of BMP4 effectively blocks the tumour growth and associated mortality that occur in 100% of mice after intracerebral grafting of human GBM cells. We demonstrate that BMPs activate their cognate receptors (BMPRs) and trigger the Smad signalling cascade in cells isolated from human glioblastomas (GBMs). This is followed by a reduction in proliferation,and increased expression of markers of neural differentiation,with no effect on cell viability. The concomitant reduction in clonogenic ability,in the size of the CD133+ population and in the growth kinetics of GBM cells indicates that BMP4 reduces the tumour-initiating cell pool of GBMs. These findings show that the BMP-BMPR signalling system--which controls the activity of normal brain stem cells--may also act as a key inhibitory regulator of tumour-initiating,stem-like cells from GBMs and the results also identify BMP4 as a novel,non-cytotoxic therapeutic effector,which may be used to prevent growth and recurrence of GBMs in humans.
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产品类型：
产品号#：
05751
产品名：
NeuroCult™ NS-A 扩增试剂盒（人）
K. B. Langer et al. (APR 2018)
Stem cell reports 10 4 1282--1293
Retinal Ganglion Cell Diversity and Subtype Specification from Human Pluripotent Stem Cells.
Retinal ganglion cells (RGCs) are the projection neurons of the retina and transmit visual information to postsynaptic targets in the brain. While this function is shared among nearly all RGCs,this class of cell is remarkably diverse,comprised of multiple subtypes. Previous efforts have identified numerous RGC subtypes in animal models,but less attention has been paid to human RGCs. Thus,efforts of this study examined the diversity of RGCs differentiated from human pluripotent stem cells (hPSCs) and characterized defined subtypes through the expression of subtype-specific markers. Further investigation of these subtypes was achieved using single-cell transcriptomics,confirming the combinatorial expression of molecular markers associated with these subtypes,and also provided insight into more subtype-specific markers. Thus,the results of this study describe the derivation of RGC subtypes from hPSCs and will support the future exploration of phenotypic and functional diversity within human RGCs.
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产品类型：
产品号#：
05790
05792
05793
05794
05795
85850
85857
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
mTeSR™1
mTeSR™1
I. Canals et al. (SEP 2018)
Nature methods 15 9 693--696
Rapid and efficient induction of functional astrocytes from human pluripotent stem cells.
The derivation of astrocytes from human pluripotent stem cells is currently slow and inefficient. We demonstrate that overexpression of the transcription factors SOX9 and NFIB in human pluripotent stem cells rapidly and efficiently yields homogeneous populations of induced astrocytes. In our study these cells exhibited molecular and functional properties resembling those of adult human astrocytes and were deemed suitable for disease modeling. Our method provides new possibilities for the study of human astrocytes in health and disease.
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Harlow DE et al. (JAN 2014)
Journal of Neuroscience 34 4 1333--1343
Expression of Proteolipid Protein Gene in Spinal Cord Stem Cells and Early Oligodendrocyte Progenitor Cells Is Dispensable for Normal Cell Migration and Myelination
Plp1 gene expression occurs very early in development,well before the onset of myelination,creating a conundrum with regard to the function of myelin proteolipid protein (PLP),one of the major proteins in compact myelin. Using PLP-EGFP mice to investigate Plp1 promoter activity,we found that,at very early time points,PLP-EGFP was expressed in Sox2+ undifferentiated precursors in the spinal cord ventricular zone (VZ),as well as in the progenitors of both neuronal and glial lineages. As development progressed,most PLP-EGFP-expressing cells gave rise to oligodendrocyte progenitor cells (OPCs). The expression of PLP-EGFP in the spinal cord was quite dynamic during development. PLP-EGFP was highly expressed as cells delaminated from the VZ. Expression was downregulated as cells moved laterally through the cord,and then robustly upregulated as OPCs differentiated into mature myelinating oligodendrocytes. The presence of PLP-EGFP expression in OPCs raises the question of its role in this migratory population. We crossed PLP-EGFP reporter mice into a Plp1-null background to investigate the role of PLP in early OPC development. In the absence of PLP,normal numbers of OPCs were generated and their distribution throughout the spinal cord was unaffected. However,the orientation and length of OPC processes during migration was abnormal in Plp1-null mice,suggesting that PLP plays a role either in the structural integrity of OPC processes or in their response to extracellular cues that orient process outgrowth.
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产品类型：
产品号#：
05707
产品名：
NeuroCult™化学解离试剂盒（小鼠）
Pei Y et al. (MAY 2016)
Brain research 1638 Pt A 57--73
Comparative neurotoxicity screening in human iPSC-derived neural stem cells, neurons and astrocytes.
Induced pluripotent stem cells (iPSC) and their differentiated derivatives offer a unique source of human primary cells for toxicity screens. Here,we report on the comparative cytotoxicity of 80 compounds (neurotoxicants,developmental neurotoxicants,and environmental compounds) in iPSC as well as isogenic iPSC-derived neural stem cells (NSC),neurons,and astrocytes. All compounds were tested over a 24-h period at 10 and 100$\$,in duplicate,with cytotoxicity measured using the MTT assay. Of the 80 compounds tested,50 induced significant cytotoxicity in at least one cell type; per cell type,32,38,46,and 41 induced significant cytotoxicity in iPSC,NSC,neurons,and astrocytes,respectively. Four compounds (valinomycin,3,3',5,5'-tetrabromobisphenol,deltamethrin,and triphenyl phosphate) were cytotoxic in all four cell types. Retesting these compounds at 1,10,and 100$\$ using the same exposure protocol yielded consistent results as compared with the primary screen. Using rotenone,we extended the testing to seven additional iPSC lines of both genders; no substantial difference in the extent of cytotoxicity was detected among the cell lines. Finally,the cytotoxicity assay was simplified by measuring luciferase activity using lineage-specific luciferase reporter iPSC lines which were generated from the parental iPSC line. This article is part of a Special Issue entitled SI: PSC and the brain.
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EasySep™小鼠TIL（CD45）正选试剂盒
产品手册qPCR Arrays for Cell Characterization
实验方案How to Culture Human Pluripotent Stem Cell (hPSC)-Derived Forebrain Neurons for MEA Analysis Using the Maestro MEA™ System
科学海报Generation of Functional 3D Spinal Cord Organoids from Human Pluripotent Stem Cells
科学海报Generation of a Glia-Neuron Co-Culture System Derived From Human Pluripotent Stem Cells
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