Kakarala M et al. (AUG 2010)
Breast cancer research and treatment 122 3 777--85
Targeting breast stem cells with the cancer preventive compounds curcumin and piperine.
The cancer stem cell hypothesis asserts that malignancies arise in tissue stem and/or progenitor cells through the dysregulation or acquisition of self-renewal. In order to determine whether the dietary polyphenols,curcumin,and piperine are able to modulate the self-renewal of normal and malignant breast stem cells,we examined the effects of these compounds on mammosphere formation,expression of the breast stem cell marker aldehyde dehydrogenase (ALDH),and Wnt signaling. Mammosphere formation assays were performed after curcumin,piperine,and control treatment in unsorted normal breast epithelial cells and normal stem and early progenitor cells,selected by ALDH positivity. Wnt signaling was examined using a Topflash assay. Both curcumin and piperine inhibited mammosphere formation,serial passaging,and percent of ALDH+ cells by 50% at 5 microM and completely at 10 microM concentration in normal and malignant breast cells. There was no effect on cellular differentiation. Wnt signaling was inhibited by both curcumin and piperine by 50% at 5 microM and completely at 10 microM. Curcumin and piperine separately,and in combination,inhibit breast stem cell self-renewal but do not cause toxicity to differentiated cells. These compounds could be potential cancer preventive agents. Mammosphere formation assays may be a quantifiable biomarker to assess cancer preventive agent efficacy and Wnt signaling assessment can be a mechanistic biomarker for use in human clinical trials.
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产品类型：
产品号#：
01700
01705
01701
01702
产品名：
ALDEFLUOR™ 试剂盒
ALDEFLUOR™ DEAB试剂, 1.5 mM, 1 mL
ALDEFLUOR™检测缓冲液
Hü et al. (JAN 2010)
International immunology 22 1 35--44
Intact LFA-1 deactivation promotes T-cell activation and rejection of cardiac allograft.
Leucocyte function-associated antigen-1 (LFA-1) is known to be involved in immune reactions leading to allograft rejection. The role of deactivating LFA-1 in this context has not been investigated yet,although it is accepted that regulating LFA-1 activity is essential for T-cell function. Expressing LFA-1 locked in an active state in mice (LFA-1(d/d)) allowed us to investigate the in vivo function of LFA-1 deactivation for allograft rejection in a model of heterotopic cardiac transplantation. We provide in vivo evidence that regulating LFA-1 activity from an active to an inactive state controls antigen-specific priming and proliferation of T cells in response to allogeneic stimuli. Consequently,defective LFA-1 deactivation significantly prolonged cardiac allograft survival. Furthermore,reduced numbers of alloantigen-specific T cells and non-allo-specific innate immune cells within allografts of LFA-1(d/d) recipients indicate that expression of active LFA-1 impairs inflammatory responses involving all major leucocyte subpopulations. Taken together,our in vivo data suggest that LFA-1 deactivation is important for the formation of inflammatory lesions and rejection of cardiac allografts. Thus,the dynamic regulation of LFA-1 activity,rather than the mere presence of LFA-1,appears to contribute to the control of immune reactions inducing allogeneic transplant rejection.
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Cited2 is an essential regulator of adult hematopoietic stem cells.
The regulatory pathways necessary for the maintenance of adult hematopoietic stem cells (HSCs) remain poorly defined. By using loss-of-function approaches,we report a selective and cell-autonomous requirement for the p300/CBP-binding transcriptional coactivator Cited2 in adult HSC maintenance. Conditional deletion of Cited2 in the adult mouse results in loss of HSCs causing multilineage bone marrow failure and increased lethality. In contrast,conditional ablation of Cited2 after lineage specification in lymphoid and myeloid lineages has no impact on the maintenance of these lineages. Additional deletion of Ink4a/Arf (encoding p16(Ink4a) and p19(Arf)) or Trp53 (encoding p53,a downstream target of p19(Arf)) in a Cited2-deficient background restores HSC functionality and rescues mice from bone marrow failure. Furthermore,we show that the critical role of Cited2 in primitive hematopoietic cells is conserved in humans. Taken together,our studies provide genetic evidence that Cited2 selectively maintains adult HSC functions,at least in part,via Ink4a/Arf and Trp53.
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产品类型：
产品号#：
70008
70008.1
70008.2
70008.3
70008.4
70008.5
70008.6
200-0002
200-0001
200-0000
产品名：
冻存的人脐带血CD34+细胞
冻存的人脐带血CD34+细胞
冻存的人脐带血CD34+细胞
冻存的人脐带血CD34+细胞
冻存的人脐带血CD34+细胞
冻存的人脐带血CD34+细胞
冻存的人脐带血CD34+细胞
冻存的人脐带血CD34+细胞
冻存的人脐带血CD34+细胞
Rovira M et al. (JAN 2010)
Proceedings of the National Academy of Sciences of the United States of America 107 1 75--80
Isolation and characterization of centroacinar/terminal ductal progenitor cells in adult mouse pancreas.
The question of whether dedicated progenitor cells exist in adult vertebrate pancreas remains controversial. Centroacinar cells and terminal duct (CA/TD) cells lie at the junction between peripheral acinar cells and the adjacent ductal epithelium,and are frequently included among cell types proposed as candidate pancreatic progenitors. However these cells have not previously been isolated in a manner that allows formal assessment of their progenitor capacities. We have found that a subset of adult CA/TD cells are characterized by high levels of ALDH1 enzymatic activity,related to high-level expression of both Aldh1a1 and Aldh1a7. This allows their isolation by FACS using a fluorogenic ALDH1 substrate. FACS-isolated CA/TD cells are relatively depleted of transcripts associated with differentiated pancreatic cell types. In contrast,they are markedly enriched for transcripts encoding Sca1,Sdf1,c-Met,Nestin,and Sox9,markers previously associated with progenitor populations in embryonic pancreas and other tissues. FACS-sorted CA/TD cells are uniquely able to form self-renewing pancreatospheres" in suspension culture�
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产品号#：
01700
01705
01701
01702
产品名：
ALDEFLUOR™ 试剂盒
ALDEFLUOR™ DEAB试剂, 1.5 mM, 1 mL
ALDEFLUOR™检测缓冲液
Sun Y et al. (MAR 2010)
Blood 115 9 1709--17
Slug deficiency enhances self-renewal of hematopoietic stem cells during hematopoietic regeneration.
Both extrinsic and intrinsic mechanisms tightly govern hematopoietic stem cell (HSC) decisions of self-renewal and differentiation. However,transcription factors that can selectively regulate HSC self-renewal division after stress remain to be identified. Slug is an evolutionarily conserved zinc-finger transcription factor that is highly expressed in primitive hematopoietic cells and is critical for the radioprotection of these key cells. We studied the effect of Slug in the regulation of HSCs in Slug-deficient mice under normal and stress conditions using serial functional assays. Here,we show that Slug deficiency does not disturb hematopoiesis or alter HSC homeostasis and differentiation in bone marrow but increases the numbers of primitive hematopoietic cells in the extramedullary spleen site. Deletion of Slug enhances HSC repopulating potential but not its homing and differentiation ability. Furthermore,Slug deficiency increases HSC proliferation and repopulating potential in vivo after myelosuppression and accelerates HSC expansion during in vitro culture. Therefore,we propose that Slug is essential for controlling the transition of HSCs from relative quiescence under steady-state condition to rapid proliferation under stress conditions. Our data suggest that inhibition of Slug in HSCs may present a novel strategy for accelerating hematopoietic recovery,thus providing therapeutic benefits for patients after clinical myelosuppressive treatment.
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产品类型：
产品号#：
09600
09650
28600
产品名：
StemSpan™ SFEM
StemSpan™ SFEM
L-Calc™有限稀释软件
Esteban MA et al. (JAN 2010)
Cell stem cell 6 1 71--9
Vitamin C enhances the generation of mouse and human induced pluripotent stem cells.
Somatic cells can be reprogrammed into induced pluripotent stem cells (iPSCs) by defined factors. However,the low efficiency and slow kinetics of the reprogramming process have hampered progress with this technology. Here we report that a natural compound,vitamin C (Vc),enhances iPSC generation from both mouse and human somatic cells. Vc acts at least in part by alleviating cell senescence,a recently identified roadblock for reprogramming. In addition,Vc accelerates gene expression changes and promotes the transition of pre-iPSC colonies to a fully reprogrammed state. Our results therefore highlight a straightforward method for improving the speed and efficiency of iPSC generation and provide additional insights into the mechanistic basis of the reprogramming process.
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Inhibition of aldehyde dehydrogenase expands hematopoietic stem cells with radioprotective capacity.
Hematopoietic stem cells (HSCs) are enriched for aldehyde dehydrogenase (ALDH) activity and ALDH is a selectable marker for human HSCs. However,the function of ALDH in HSC biology is not well understood. We sought to determine the function of ALDH in regulating HSC fate. Pharmacologic inhibition of ALDH with diethylaminobenzaldehyde (DEAB) impeded the differentiation of murine CD34(-)c-kit(+)Sca-1(+)lineage(-) (34(-)KSL) HSCs in culture and facilitated a ninefold expansion of cells capable of radioprotecting lethally irradiated mice compared to input 34(-)KSL cells. Treatment of bone marrow (BM) 34(-)KSL cells with DEAB caused a fourfold increase in 4-week competitive repopulating units,verifying the amplification of short-term HSCs (ST-HSCs) in response to ALDH inhibition. Targeted siRNA of ALDH1a1 in BM HSCs caused a comparable expansion of radioprotective progenitor cells in culture compared to DEAB treatment,confirming that ALDH1a1 was the target of DEAB inhibition. The addition of all trans retinoic acid blocked DEAB-mediated expansion of ST-HSCs in culture,suggesting that ALDH1a1 regulates HSC differentiation via augmentation of retinoid signaling. Pharmacologic inhibition of ALDH has therapeutic potential as a means to amplify ST-HSCs for transplantation purposes.
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产品类型：
产品号#：
01700
01705
01701
01702
产品名：
ALDEFLUOR™ 试剂盒
ALDEFLUOR™ DEAB试剂, 1.5 mM, 1 mL
ALDEFLUOR™检测缓冲液
Jeselsohn R et al. (JAN 2010)
Cancer cell 17 1 65--76
Cyclin D1 kinase activity is required for the self-renewal of mammary stem and progenitor cells that are targets of MMTV-ErbB2 tumorigenesis.
Transplantation studies have demonstrated the existence of mammary progenitor cells with the ability to self-renew and regenerate a functional mammary gland. Although these progenitors are the likely targets for oncogenic transformation,correlating progenitor populations with certain oncogenic stimuli has been difficult. Cyclin D1 is required for lobuloalveolar development during pregnancy and lactation as well as MMTV-ErbB2- but not MMTV-Wnt1-mediated tumorigenesis. Using a kinase-deficient cyclin D1 mouse,we identified two functional mammary progenitor cell populations,one of which is the target of MMTV-ErbB2. Moreover,cyclin D1 activity is required for the self-renewal and differentiation of mammary progenitors because its abrogation leads to a failure to maintain the mammary epithelial regenerative potential and also results in defects in luminal lineage differentiation.
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产品类型：
产品号#：
19757
产品名：
Naka K et al. (FEB 2010)
Nature 463 7281 676--80
TGF-beta-FOXO signalling maintains leukaemia-initiating cells in chronic myeloid leukaemia.
Chronic myeloid leukaemia (CML) is caused by a defined genetic abnormality that generates BCR-ABL,a constitutively active tyrosine kinase. It is widely believed that BCR-ABL activates Akt signalling that suppresses the forkhead O transcription factors (FOXO),supporting the proliferation or inhibiting the apoptosis of CML cells. Although the use of the tyrosine kinase inhibitor imatinib is a breakthrough for CML therapy,imatinib does not deplete the leukaemia-initiating cells (LICs) that drive the recurrence of CML. Here,using a syngeneic transplantation system and a CML-like myeloproliferative disease mouse model,we show that Foxo3a has an essential role in the maintenance of CML LICs. We find that cells with nuclear localization of Foxo3a and decreased Akt phosphorylation are enriched in the LIC population. Serial transplantation of LICs generated from Foxo3a(+/+) and Foxo3a(-/-) mice shows that the ability of LICs to cause disease is significantly decreased by Foxo3a deficiency. Furthermore,we find that TGF-beta is a critical regulator of Akt activation in LICs and controls Foxo3a localization. A combination of TGF-beta inhibition,Foxo3a deficiency and imatinib treatment led to efficient depletion of CML in vivo. Furthermore,the treatment of human CML LICs with a TGF-beta inhibitor impaired their colony-forming ability in vitro. Our results demonstrate a critical role for the TGF-beta-FOXO pathway in the maintenance of LICs,and strengthen our understanding of the mechanisms that specifically maintain CML LICs in vivo.
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产品类型：
产品号#：
72592
产品名：
LY364947
Sugii S et al. (FEB 2010)
Proceedings of the National Academy of Sciences of the United States of America 107 8 3558--63
Human and mouse adipose-derived cells support feeder-independent induction of pluripotent stem cells.
Although adipose tissue is an expandable and readily attainable source of proliferating,multipotent stem cells,its potential for use in regenerative medicine has not been extensively explored. Here we report that adult human and mouse adipose-derived stem cells can be reprogrammed to induced pluripotent stem (iPS) cells with substantially higher efficiencies than those reported for human and mouse fibroblasts. Unexpectedly,both human and mouse iPS cells can be obtained in feeder-free conditions. We discovered that adipose-derived stem cells intrinsically express high levels of pluripotency factors such as basic FGF,TGFbeta,fibronectin,and vitronectin and can serve as feeders for both autologous and heterologous pluripotent cells. These results demonstrate a great potential for adipose-derived cells in regenerative therapeutics and as a model for studying the molecular mechanisms of feeder-free iPS generation and maintenance.
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产品类型：
产品号#：
05850
05857
05870
05875
85850
85857
85870
85875
产品名：
mTeSR™1
mTeSR™1
Agarwal S et al. (MAR 2010)
Nature 464 7286 292--6
Telomere elongation in induced pluripotent stem cells from dyskeratosis congenita patients.
Patients with dyskeratosis congenita (DC),a disorder of telomere maintenance,suffer degeneration of multiple tissues. Patient-specific induced pluripotent stem (iPS) cells represent invaluable in vitro models for human degenerative disorders like DC. A cardinal feature of iPS cells is acquisition of indefinite self-renewal capacity,which is accompanied by induction of the telomerase reverse transcriptase gene (TERT). We investigated whether defects in telomerase function would limit derivation and maintenance of iPS cells from patients with DC. Here we show that reprogrammed DC cells overcome a critical limitation in telomerase RNA component (TERC) levels to restore telomere maintenance and self-renewal. We discovered that TERC upregulation is a feature of the pluripotent state,that several telomerase components are targeted by pluripotency-associated transcription factors,and that in autosomal dominant DC,transcriptional silencing accompanies a 3' deletion at the TERC locus. Our results demonstrate that reprogramming restores telomere elongation in DC cells despite genetic lesions affecting telomerase,and show that strategies to increase TERC expression may be therapeutically beneficial in DC patients.
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产品类型：
产品号#：
05850
05857
05870
05875
85850
85857
85870
85875
产品名：
mTeSR™1
mTeSR™1
Fang Y et al. (JUN 2010)
Journal of leukocyte biology 87 6 1019--28
Comparison of sensitivity of Th1, Th2, and Th17 cells to Fas-mediated apoptosis.
Following activation through the TCR,CD4+ T cells can differentiate into three major subsets: Th1,Th2,and Th17 cells. IL-17-secreting Th17 cells play an important role in the pathogenesis of several autoimmune diseases and in immune responses to pathogens,but little is known about the regulation of apoptosis in Th17 cells. In this study,the sensitivity of in vitro-polarized Th1,Th2,and Th17 cells to Fas-mediated apoptosis was compared directly by different methods. The order of sensitivity of T cell subsets to Fas-mediated apoptosis is: Th1 textgreater Th17 textgreater Th2. The greater sensitivity of Th17 cells to Fas-mediated apoptosis compared with Th2 cells correlated with their higher expression of FasL and comparable expression of the antiapoptotic molecule FLIP. The decreased sensitivity of Th17 compared with Th1 cells correlated with the higher expression of FLIP by Th17 cells. Transgenic overexpression of FLIP in T cells protected all three subsets from Fas-mediated apoptosis. These findings provide new knowledge for understanding how survival of different subsets of T cells is regulated.
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