参考文献

Tian L et al. (APR 2016) Stem Cell Reviews and Reports 12 4 500--508

Efficient and Controlled Generation of 2D and 3D Bile Duct Tissue from Human Pluripotent Stem Cell-Derived Spheroids

While in vitro liver tissue engineering has been increasingly studied during the last several years,presently engineered liver tissues lack the bile duct system. The lack of bile drainage not only hinders essential digestive functions of the liver,but also leads to accumulation of bile that is toxic to hepatocytes and known to cause liver cirrhosis. Clearly,generation of bile duct tissue is essential for engineering functional and healthy liver. Differentiation of human induced pluripotent stem cells (iPSCs) to bile duct tissue requires long and/or complex culture conditions,and has been inefficient so far. Towards generating a fully functional liver containing biliary system,we have developed defined and controlled conditions for efficient 2D and 3D bile duct epithelial tissue generation. A marker for multipotent liver progenitor in both adult human liver and ductal plate in human fetal liver,EpCAM,is highly expressed in hepatic spheroids generated from human iPSCs. The EpCAM high hepatic spheroids can,not only efficiently generate a monolayer of biliary epithelial cells (cholangiocytes),in a 2D differentiation condition,but also form functional ductal structures in a 3D condition. Importantly,this EpCAM high spheroid based biliary tissue generation is significantly faster than other existing methods and does not require cell sorting. In addition,we show that a knock-in CK7 reporter human iPSC line generated by CRISPR/Cas9 genome editing technology greatly facilitates the analysis of biliary differentiation. This new ductal differentiation method will provide a more efficient method of obtaining bile duct cells and tissues,which may facilitate engineering of complete and functional liver tissue in the future. View Publication

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05850

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产品名：

mTeSR™1

Robinson M et al. (AUG 2016) Stem Cell Reviews and Reports 12 4 476--483

Functionalizing Ascl1 with Novel Intracellular Protein Delivery Technology for Promoting Neuronal Differentiation of Human Induced Pluripotent Stem Cells

Pluripotent stem cells can become any cell type found in the body. Accordingly,one of the major challenges when working with pluripotent stem cells is producing a highly homogenous population of differentiated cells,which can then be used for downstream applications such as cell therapies or drug screening. The transcription factor Ascl1 plays a key role in neural development and previous work has shown that Ascl1 overexpression using viral vectors can reprogram fibroblasts directly into neurons. Here we report on how a recombinant version of the Ascl1 protein functionalized with intracellular protein delivery technology (Ascl1-IPTD) can be used to rapidly differentiate human induced pluripotent stem cells (hiPSCs) into neurons. We first evaluated a range of Ascl1-IPTD concentrations to determine the most effective amount for generating neurons from hiPSCs cultured in serum free media. Next,we looked at the frequency of Ascl1-IPTD supplementation in the media on differentiation and found that one time supplementation is sufficient enough to trigger the neural differentiation process. Ascl1-IPTD was efficiently taken up by the hiPSCs and enabled rapid differentiation into TUJ1-positive and NeuN-positive populations with neuronal morphology after 8 days. After 12 days of culture,hiPSC-derived neurons produced by Ascl1-IPTD treatment exhibited greater neurite length and higher numbers of branch points compared to neurons derived using a standard neural progenitor differentiation protocol. This work validates Ascl1-IPTD as a powerful tool for engineering neural tissue from pluripotent stem cells. View Publication

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05832

05833

05838

05872

05873

05940

07174

07180

07183

07190

27147

07191

36254

07930

07931

07940

07955

07956

07959

07954

27845

27945

27840

27865

27940

27965

05835

05839

08581

08582

100-0483

100-0484

100-1061

07952

100-0763

100-0485

100-1077

产品名：

STEMdiff™ 神经花环选择试剂

STEMdiff™神经前体细胞培养基

STEMdiff™神经祖细胞冻存液

Vitronectin XF™

CellAdhere™ 稀释缓冲液

DMEM/F-12 with 15 mM HEPES

CryoStor® CS10

STEMdiff™ 神经诱导培养基

STEMdiff™SMADi神经诱导试剂盒

STEMdiff™SMADi神经诱导试剂盒，2套

Hausser Scientificᵀᴹ 明线血球计数板

ReLeSR™

CryoStor® CS10

Vitronectin XF™

温和细胞解离试剂

ReLeSR™

Wang W et al. (MAY 2016) Cell 165 5 1092--105

Effector T Cells Abrogate Stroma-Mediated Chemoresistance in Ovarian Cancer.

Effector T cells and fibroblasts are major components in the tumor microenvironment. The means through which these cellular interactions affect chemoresistance is unclear. Here,we show that fibroblasts diminish nuclear accumulation of platinum in ovarian cancer cells,resulting in resistance to platinum-based chemotherapy. We demonstrate that glutathione and cysteine released by fibroblasts contribute to this resistance. CD8(+) T cells abolish the resistance by altering glutathione and cystine metabolism in fibroblasts. CD8(+) T-cell-derived interferon (IFN)γ controls fibroblast glutathione and cysteine through upregulation of gamma-glutamyltransferases and transcriptional repression of system xc(-) cystine and glutamate antiporter via the JAK/STAT1 pathway. The presence of stromal fibroblasts and CD8(+) T cells is negatively and positively associated with ovarian cancer patient survival,respectively. Thus,our work uncovers a mode of action for effector T cells: they abrogate stromal-mediated chemoresistance. Capitalizing upon the interplay between chemotherapy and immunotherapy holds high potential for cancer treatment. View Publication

产品号#：

17953

17953RF

15022

15062

100-0710

产品名：

EasySep™人CD8+ T细胞分选试剂盒

RoboSep™ 人CD8+ T细胞分选试剂盒

RosetteSep™人CD4+ T细胞富集抗体混合物

EasySep™人CD8+ T细胞分选试剂盒

Lowe A et al. (MAY 2016) Stem Cell Reports 6 5 743--756

Intercellular Adhesion-Dependent Cell Survival and ROCK-Regulated Actomyosin-Driven Forces Mediate Self-Formation of a Retinal Organoid

In this study we dissected retinal organoid morphogenesis in human embryonic stem cell (hESC)-derived cultures and established a convenient method for isolating large quantities of retinal organoids for modeling human retinal development and disease. Epithelialized cysts were generated via floating culture of clumps of Matrigel/hESCs. Upon spontaneous attachment and spreading of the cysts,patterned retinal monolayers with tight junctions formed. Dispase-mediated detachment of the monolayers and subsequent floating culture led to self-formation of retinal organoids comprising patterned neuroretina,ciliary margin,and retinal pigment epithelium. Intercellular adhesion-dependent cell survival and ROCK-regulated actomyosin-driven forces are required for the self-organization. Our data supports a hypothesis that newly specified neuroretina progenitors form characteristic structures in equilibrium through minimization of cell surface tension. In long-term culture,the retinal organoids autonomously generated stratified retinal tissues,including photoreceptors with ultrastructure of outer segments. Our system requires minimal manual manipulation,has been validated in two lines of human pluripotent stem cells,and provides insight into optic cup invagination in vivo. View Publication

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05850

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100-0483

100-0484

产品名：

mTeSR™1

Hausser Scientificᵀᴹ 明线血球计数板

ReLeSR™

Nazareth EJP et al. (MAY 2016) Stem cell reports 6 5 679--91

A Multi-Lineage Screen Reveals mTORC1 Inhibition Enhances Human Pluripotent Stem Cell Mesendoderm and Blood Progenitor Production.

Human pluripotent stem cells (hPSCs) exist in heterogeneous micro-environments with multiple subpopulations,convoluting fate-regulation analysis. We patterned hPSCs into engineered micro-environments and screened responses to 400 small-molecule kinase inhibitors,measuring yield and purity outputs of undifferentiated,neuroectoderm,mesendoderm,and extra-embryonic populations. Enrichment analysis revealed mammalian target of rapamycin (mTOR) inhibition as a strong inducer of mesendoderm. Dose responses of mTOR inhibitors such as rapamycin synergized with Bone Morphogenetic protein 4 (BMP4) and activin A to enhance the yield and purity of BRACHYURY-expressing cells. Mechanistically,small interfering RNA knockdown of RAPTOR,a component of mTOR complex 1,phenocopied the mesendoderm-enhancing effects of rapamycin. Functional analysis during mesoderm and endoderm differentiation revealed that mTOR inhibition increased the output of hemogenic endothelial cells 3-fold,with a concomitant enhancement of blood colony-forming cells. These data demonstrate the power of our multi-lineage screening approach and identify mTOR signaling as a node in hPSC differentiation to mesendoderm and its derivatives. View Publication

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mTeSR™1

Li D et al. (MAY 2016) Stem Cell Reports 6 5 717--728

Optimized Approaches for Generation of Integration-free iPSCs from Human Urine-Derived Cells with Small Molecules and Autologous Feeder

Generation of induced pluripotent stem cells (iPSCs) from human urine-derived cells (hUCs) provides a convenient and non-invasive way to obtain patient-specific iPSCs. However,many isolated hUCs exhibit very poor proliferation and are difficult to reprogram. In this study,we optimized reprogramming approaches for hUCs with very poor proliferation. We report here that a compound cocktail containing cyclic pifithrin-a (a P53 inhibitor),A-83-01,CHIR99021,thiazovivin,NaB,and PD0325901 significantly improves the reprogramming efficiency (170-fold more) for hUCs. In addition,we showed that replacement of Matrigel with autologous hUC feeders can overcome the reprogramming failure due to the massive cell death that occurs during delivery of reprogramming factors. In summary,we describe improved approaches to enable iPSC generation from hUCs that were otherwise difficult to reprogram,a valuable asset for banking patient-specific iPSCs. View Publication

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05850

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mTeSR™1

Stanford EA et al. (APR 2016) Molecular cancer research : MCR

Role for the Aryl Hydrocarbon Receptor and Diverse Ligands In Oral Squamous Cell Carcinoma Migration and Tumorigenesis.

Over 45,000 new cases of oral and pharyngeal cancers are diagnosed and account for over 8,000 deaths a year in the United States. An environmental chemical receptor,the aryl hydrocarbon receptor (AHR),has previously been implicated in oral squamous cell carcinoma (OSCC) initiation as well as in normal tissue-specific stem cell self-renewal. These previous studies inspired the hypothesis that the AHR plays a role in both the acquisition and progression of OSCC,as well as in the formation and maintenance of cancer stem-like cells. To test this hypothesis,AHR activity in two oral squamous cell lines was modulated with AHR prototypic,environmental and bacterial AHR ligands,AHR-specific inhibitors,and phenotypic,genomic and functional characteristics were evaluated. The data demonstrate that: 1) primary OSCC tissue expresses elevated levels of nuclear AHR as compared to normal tissue,2) Ahr mRNA expression is up-regulated in 320 primary OSCC,3) AHR hyper-activation with several ligands,including environmental and bacterial ligands,significantly increases AHR activity,ALDH1 activity,and accelerates cell migration,4) AHR inhibition blocks the rapid migration of OSCC cells and reduces cell chemoresistance,5) AHR knockdown inhibits tumorsphere formation in low adherence conditions,and 6) AHR knockdown inhibits tumor growth and increases overall survival in vivo. These data demonstrate that the AHR plays an important role in development and progression of OSCC,and specifically cancer stem-like cells. Prototypic,environmental and bacterial AHR ligands may exacerbate OSCC by enhancing expression of these properties. IMPLICATIONS This study,for the first time,demonstrates the ability of diverse AHR ligands to regulate AHR activity in oral squamous cell carcinoma cells,as well as regulate several important characteristics of oral cancer stem cells,in vivo and in vitro. View Publication

产品号#：

05620

产品名：

MammoCult™人培养基试剂盒

Sun Y et al. (MAY 2016) mBio 7 2 e00465--16

Deletion of a Yci1 Domain Protein of Candida albicans Allows Homothallic Mating in MTL Heterozygous Cells

It has been proposed that the ancestral fungus was mating competent and homothallic. However,many mating-competent fungi were initially classified as asexual because their mating capacity was hidden behind layers of regulation. For efficient in vitro mating,the essentially obligate diploid ascomycete pathogen Candida albicans has to change its mating type locus from heterozygous MTL a /α to homozygous MTL a / a or MTL α/α and then undergo an environmentally controlled epigenetic switch to the mating-competent opaque form. These requirements greatly reduce the potential for C. albicans mating. Deletion of the Yci1 domain gene OFR1 bypasses the need for C. albicans cells to change the mating type locus from heterozygous to homozygous prior to switching to the opaque form and mating and allows homothallic mating of MTL heterozygous strains. This bypass is carbon source dependent and does not occur when cells are grown on glucose. Transcriptional profiling of ofr1 mutant cells shows that in addition to regulating cell type and mating circuitry,Ofr1 is needed for proper regulation of histone and chitin biosynthesis gene expression. It appears that OFR1 is a key regulator in C. albicans and functions in part to maintain the cryptic mating phenotype of the pathogen. View Publication

产品号#：

03800

03801

03802

03803

03804

03805

03806

产品名：

ClonaCell™-HY 杂交瘤试剂盒

ClonaCell™-HY Medium

ClonaCell™-HY PEG (融合)

Ohne Y et al. (JUN 2016) Nature immunology 17 6 646--55

IL-1 is a critical regulator of group 2 innate lymphoid cell function and plasticity.

Group 2 innate lymphoid cells (ILC2 cells) are important for type 2 immune responses and are activated by the epithelial cytokines interleukin 33 (IL-33),IL-25 and thymic stromal lymphopoietin (TSLP). Here we demonstrated that IL-1β was a critical activator of ILC2 cells,inducing proliferation and cytokine production and regulating the expression of epithelial cytokine receptors. IL-1β also governed ILC2 plasticity by inducing low expression of the transcription factor T-bet and the cytokine receptor chain IL-12Rβ2,which enabled the conversion of these cells into an ILC1 phenotype in response to IL-12. This transition was marked by an atypical chromatin landscape characterized by the simultaneous transcriptional accessibility of the locus encoding interferon-γ (IFN-γ) and the loci encoding IL-5 and IL-13. Finally,IL-1β potentiated ILC2 activation and plasticity in vivo,and IL-12 acted as the switch that determined an ILC2-versus-ILC1 response. Thus,we have identified a previously unknown role for IL-1β in facilitating ILC2 maturation and plasticity. View Publication

产品号#：

19055

19055RF

15025

15065

产品名：

EasySep™人NK细胞富集试剂盒

RoboSep™ 人NK细胞富集试剂盒含滤芯吸头

RosetteSep™人NK细胞富集抗体混合物

Douvaras P et al. ( 2016) International Journal of Molecular Sciences 17 4

Epigenetic modulation of human induced pluripotent stem cell differentiation to oligodendrocytes

Pluripotent stem cells provide an invaluable tool for generating human,disease-relevant cells. Multiple sclerosis is an inflammatory demyelinating disease of the central nervous system,characterized by myelin damage. Oligodendrocytes are the myelinating cells of the central nervous system (CNS); they differentiate from progenitor cells,and their membranes ensheath axons,providing trophic support and allowing fast conduction velocity. The current understanding of oligodendrocyte biology was founded by rodent studies,where the establishment of repressive epigenetic marks on histone proteins,followed by activation of myelin genes,leads to lineage progression. To assess whether this epigenetic regulation is conserved across species,we differentiated human embryonic and induced pluripotent stem cells to oligodendrocytes and asked whether similar histone marks and relative enzymatic activities could be detected. The transcriptional levels of enzymes responsible for methylation and acetylation of histone marks were analyzed during oligodendrocyte differentiation,and the post-translational modifications on histones were detected using immunofluorescence. These studies showed that also in human cells,differentiation along the oligodendrocyte lineage is characterized by the acquisition of multiple repressive histone marks,including deacetylation of lysine residues on histone H3 and trimethylation of residues K9 and K27. These data suggest that the epigenetic modulation of oligodendrocyte identity is highly conserved across species. View Publication

产品号#：

05850

05857

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85850

85857

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产品名：

mTeSR™1

Efficient and Controlled Generation of 2D and 3D Bile Duct Tissue from Human Pluripotent Stem Cell-Derived Spheroids

Functionalizing Ascl1 with Novel Intracellular Protein Delivery Technology for Promoting Neuronal Differentiation of Human Induced Pluripotent Stem Cells

Effector T Cells Abrogate Stroma-Mediated Chemoresistance in Ovarian Cancer.

Intercellular Adhesion-Dependent Cell Survival and ROCK-Regulated Actomyosin-Driven Forces Mediate Self-Formation of a Retinal Organoid

A Multi-Lineage Screen Reveals mTORC1 Inhibition Enhances Human Pluripotent Stem Cell Mesendoderm and Blood Progenitor Production.

Optimized Approaches for Generation of Integration-free iPSCs from Human Urine-Derived Cells with Small Molecules and Autologous Feeder

Role for the Aryl Hydrocarbon Receptor and Diverse Ligands In Oral Squamous Cell Carcinoma Migration and Tumorigenesis.

Deletion of a Yci1 Domain Protein of Candida albicans Allows Homothallic Mating in MTL Heterozygous Cells

IL-1 is a critical regulator of group 2 innate lymphoid cell function and plasticity.

Epigenetic modulation of human induced pluripotent stem cell differentiation to oligodendrocytes

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