When applied to diverse tissue types and organisms, CytoTRACE outperformed previous methods and nearly 19,000 annotated gene sets for resolving 52 experimentally determined developmental trajectories. Clarke, M. F., Clevers, H., Eaves, C. J., Weinberg, R. A., Rajasekhar, V. K. Quantitative assessment of single-cell RNA-sequencing methods. van Weele, L. J., Djomehri, S. I., Cai, S., Antony, J., Sikandar, S. S., Qian, D., Ho, W. H., West, R., Scheeren, F. A., Clarke, M. F. Publisher Correction: Cell types of origin of the cell-free transcriptome. We developed a new technique that replaces immunoprecipitation with a simplified chromatin fragmentation and proximity ligation step that eliminates bead purification and washing steps. All together, these findings link important stem cell regulators like Bmi1/Usp16 and Cdkn2a to Wnt signaling, and have implications for designing therapies for conditions, like DS, aging or degenerative diseases, where the Wnt pathway is hampered. Flow cytometry and microfluidics-based single-cell multiplex RT-PCR allowed dissection of IFN responses in single RV-infected and bystander intestinal epithelial cells (IECs). Even in the absence of an exogenous apoptotic signal such as x-irradiation, this virus specifically and efficiently kills carcinoma cells arising from multiple organs including breast, colon, stomach, and neuroblasts. With the growing evidence that cancer stem cells exist in a wide array of tumors, it is becoming increasingly important to understand the molecular mechanisms that regulate self-renewal and differentiation because corruption of genes involved in these pathways likely participates in tumor growth. James Mallet (* 1955), Evolutionsbiologe und Entomologe. Using a model in which human breast cancer cells were grown in immunocompromised mice, we found that only a minority of breast cancer cells had the ability to form new tumors. View details for DOI 10.1371/journal.pone.0002428, View details for Web of Science ID 000263280700013, View details for PubMedCentralID PMC2413402, View details for Web of Science ID 000454834700190. Upon transfer to 32.5 degrees C, these G1 synchronized cell populations quickly lost viability. Thus, the development of proper sampling techniques or improved stem cell retention may be critical to obtain successful long-term cultures. Sen, A., Rothenberg, M. E., Mukherjee, G., Feng, N., Kalisky, T., Nair, N., Johnstone, I. M., Clarke, M. F., Greenberg, H. B. Remodeling of Endogenous Mammary Epithelium by Breast Cancer Stem Cells. Dalerba, P., Sahoo, D., Paik, S., Guo, X., Yothers, G., Song, N., Wilcox-Fogel, N., Forgo, E., Rajendran, P. S., Miranda, S. P., Hisamori, S., Hutchison, J., Kalisky, T., Qian, D., Wolmark, N., Fisher, G. A., van de Rijn, M., Clarke, M. F. CDX2 as a Prognostic Biomarker in Stage II and Stage III Colon Cancer. Cai, S., Kalisky, T., Sahoo, D., Dalerba, P., Feng, W., Lin, Y., Qian, D., Kong, A., Yu, J., Wang, F., Chen, E. Y., Scheeren, F. A., Kuo, A. H., Sikandar, S. S., Hisamori, S., van Weele, L. J., Heiser, D., Sim, S., Lam, J., Quake, S., Clarke, M. F. Targeted chromatin ligation, a robust epigenetic profiling technique for small cell numbers. Diehn, M., Cho, R. W., Ailles, L., Lam, J. S., Kaplan, M. J., Somlo, G., Weissman, I. L., Clarke, M. F. Implications of Cancer Stem Cells for Tumor Metastasis. View details for DOI 10.1196/annals.1349.012, View details for Web of Science ID 000230894100011, View details for Web of Science ID 000225161400025. Just months into the Biden-Harris administration, the change in tone, message, and approach to transatlantic relations is palpable. Analysis of DNase I cutting of uniquely end-labeled complexes suggests that the fragment containing a single 72-bp element forms a positioned core particle. In both breast cancers and central nervous system tumors, cancer cells differ in their ability to form tumors. All measured metabolic rates increased with increased medium exchange rates and accelerated sharply between exchange rates of 3.5/week and 7/week. The telomerase reverse transcriptase (TERT) promoter and the E2F-1 promoter are preferentially activated in cancer cells. We studied the effect of the combination of rapid culture medium exchange with the addition of the human hematopoietic growth factors interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), and erythropoietin (Epo) on the proliferation and differentiation of human long-term bone marrow cultures (LTBMCs). Genomic DNA extracted at 32.5 degrees C was seen to be fragmented into a characteristic ladder consistent with cell death due to apoptosis. Michael W. Clark is the Director of the Center for Business and Economic Research and an Associate Professor of Economics at the University of Kentucky's Gatton College of Business and Economics. Control cultures that were exposed to conCM after 4 weeks in culture significantly improved their cell productivity during the latter 4 weeks of culture compared with control. One such cDNA clone, KT1, was isolated and its nucleotide sequence was determined. Two distinct technical approaches were used for most organs: one approach, microfluidic droplet-based 3'-end counting, enabled the survey of thousands of cells at relatively low coverage, whereas the other, full-length transcript analysis based on fluorescence-activated cell sorting, enabled the characterization of cell types with high sensitivity and coverage. Han, J. S., Nunez, G., Wicha, M. S., Clarke, M. F. Prevention of fluorodeoxyuridine-induced cytotoxicity and DNA damage in HT29 colon carcinoma cells by conditional expression of wild-type p53 phenotype. A growing body of evidence indicates that subpopulations of cancer stem cells (CSCs) drive and maintain many types of human malignancies. erenakgun@g.harvard.edu. (2007) analyze the relationship between CSC and tumor metastasis. Professor Michael Clarke, former director of the defence think tank Rusi said: "Often these symbols will be location-based - they will be communicating where a unit is heading. View details for Web of Science ID A1996VX88000036, View details for Web of Science ID A1996VT98300744. View details for DOI 10.1016/j.stem.2007.08.012, View details for Web of Science ID 000251055200003. Room 424:1 Advanced Engineering Building (49) . Within 24-48 hr, viral RNA expression increased at least four- to eightfold. We performed multiplexed single-cell gene expression analysis with quantitative reverse transcriptase polymerase chain reaction followed by hierarchical clustering analysis to characterize distinct cell types. Lobo, N. A., Zabala, M., Qian, D., Clarke, M. F. Serially transplantable mammary epithelial cells express the Thy-1 antigen. View details for Web of Science ID 000168861600008. Constitutive expression of mbm2, in contrast to c-myb, here resulted in enhanced differentiation of F-MEL cells. This suggests RGS18 can act on G(q)-mediated signaling pathways in vivo. ANGELOTTI, T. P., Clarke, M. F., Longino, M. A., Emerson, S. G. THE CONSTRUCTION OF HIGH-EFFICIENCY HUMAN BONE-MARROW TISSUE EXVIVO. A., Issa, J., Clarke, M. F., Look, A. T. Lobo, N. A., Shimono, Y., Qian, D., Clarke, M. F. Cancer stem cells and radiotherapy: New insights into tumor radioresistance. MMTV-Wnt-1 breast tumors were harvested, dissociated into single-cell suspensions, and sorted by flow cytometry on Thy1, CD24, and CD45. Akala, O. O., Park, I., Qian, D., Pihalja, M., Becker, M. W., Clarke, M. F. A gene signature in breast cancer - Reply. View details for DOI 10.1002/1878-0261.13220, View details for DOI 10.1038/s41587-022-01293-3. Mann, D. L., Clark, J., Clarke, M., Reitz, M., Popovic, M., Franchini, G., Trainor, C. D., STRONG, D. M., Blattner, W. A., Gallo, R. C. Presence of HTLV in a subset of T cells from an infected patient: some immunochemical properties of the infected cells. This functional subset of cancer cells is operationally defined as the "cancer stem cell" (CSC) subset. Analysis of the surface molecule repertoire of EpCAM(high)/CD44+ cells led to the identification of CD166 as an additional differentially expressed marker, useful for CSC isolation in three of three CRC tested. Dalerba, P., Sahoo, D., Paik, S., Guo, X., Yothers, G., Song, N., Wilcox-Fogel, N., Forg, E., Rajendran, P. S., Miranda, S. P., Hisamori, S., Hutchison, J., Kalisky, T., Qian, D., Wolmark, N., Fisher, G. A., van de Rijn, M., Clarke, M. F. A cell-intrinsic role for TLR2-MYD88 in intestinal and breast epithelia and oncogenesis. Cancers of epithelial origin are responsible for the majority of cancer-related deaths in the USA. We prospectively identified and isolated the tumorigenic cells as CD44(+)CD24(-/low)Lineage(-) in eight of nine patients. Breast cancer is the most common malignancy in United States women, accounting for >40,000 deaths each year. Since only a portion of the cells in culture expressed Ig light chains, experiments were carried out to exclude the possibility that the cultures were not a mixture of B and T or non-B cells. In normal mouse epithelium, LEFTY1 expression in a subset of luminal cells and rare basal cells opposes BMP7 to promote ductal branching. Stem cell biology has come of age. War in Ukraine 2022: Prof. Michael Clarke analysis 116 videos 3,380 views Updated 5 days ago Defence and security analyst Professor Michael Clarke's observations mostly on Sky News. View details for DOI 10.1073/pnas.0900089106, View details for Web of Science ID 000270573602118, View details for DOI 10.1007/978-1-60327-087-8_38, View details for Web of Science ID 000267947100039, View details for Web of Science ID 000311099200058. Limited viral replication facilitates greater penetration of virions into tissue and can improve gene transfer. Disease status (no. Although major categories of ageing damage have been identified-such as altered intercellular communication, loss of proteostasis and eroded mitochondrial function1-these deleterious processes interact with extraordinary complexity within and between organs, and a comprehensive, whole-organism analysis of ageing dynamics has been lacking. Here, using molecular clones of HTLV and human major histocompatibility antigen DNA, we have shown homology between the envelope gene region of HTLV and the region of an HLA-B locus gene which codes for the extracellular portion of a class I histocompatibility antigen. Cytoplasmic sequestration of the p53 tumor suppresser protein has been proposed as a mechanism involved in abolishing p53 function. Professor Michael Clarke was Director-General of the Royal United Services Institute (RUSI) from 2007 to 2015 when he retired from that role. These findings demonstrate that p53 overexpression renders Shep-1 cells IR-sensitive and suggest that large quantities of exogenous p53 can overcome the factors inhibiting p53-mediated, IR-induced apoptosis. Unfortunately, although chemotherapy and/or radiation therapy can sometimes shrink tumors, metastatic cancers of epithelial origin are essentially incurable. A full-length human c-myb cDNA clone has been isolated from a CCRF-CEM leukemia cell cDNA library. Taken together, these results suggest that Bcl11b acts as acentral intrinsic regulator of mammary epithelial stem cell quiescence and exhaustion and is necessary for long-term maintenance of the mammary gland. This demands a complex crosstalk between extrinsic signals from the microenvironment and the cell-intrinsic regulators of self-renewal. By complementation of the E1a protein in trans, Ad5ERE2 allows restricted replication of a conventional E1a-deleted adenoviral vector. We have examined the respiratory burst and arachidonic acid oxygenation that accompany phagocytosis in macrophages. Under these conditions, the cultures produced as many cells as were inoculated every 2 weeks and led to a greater than 2.5-fold expansion in terms of the number of nonadherent cells produced over a 6- to 8-week period. Yoo, S., Chandhasin, C., Del Rosario, J., Chen, Y. K., Stafford, J., Perabo, F., Clarke, M. F. Inhibition of histone lysine demethylases with TACH101, a first-in-class pan-inhibitor of KDM4. Nuovo ateismo o neo-ateismo, anche nella grafia neoateismo (in inglese New Atheism), una corrente di pensiero che raccoglie le posizioni promosse da alcuni atei del XXI secolo. Our metastatic cancer models, combined with noninvasive imaging techniques, constitute an integrated approach that could be applied to dissect the molecular mechanisms underlying the dissemination of metastatic CSCs (MCSCs) and to explore therapeutic strategies targeting MCSCs in general or to evaluate individual patient tumor cells and predict response to therapy. View details for Web of Science ID A1995RP92400014. The wild-type p53/GFP fusion protein was localized in the cytoplasm, the nucleus, or both compartments in a subset of the cells. Professor Michael Clarke was Director-General of the Royal United Services Institute (RUSI) from 2007 to 2015 when he retired from that role. G418-resistant clones, which expressed the c-sis cDNA, were selected and characterized. Thomas Jeffrey Hanks ( Concord, California; 9 de julio de 1956) es un actor y director de cine estadounidense. These advances in BCSC imaging revealed that CD44(+) cells from both primary tumors and lung metastases are highly enriched for tumor-initiating cells. Although cancer cell lines provide invaluable information, their biological properties often differ in crucial ways from de novo cancer cells. These include the nuclear import and export signals of p53, inhibition of p53 nuclear import and export by oligomerization, MDM2-mediated p53 nuclear export, and possible roles of p53 phosphorylation in regulating p53 cellular localization. Access is controlled by the 1936 Montreux Convention that gives Turkey the right to close the straits in times of war. In the mammary gland, the identity and characteristics of quiescent epithelial stem cells are not clear. The arrangement of this clone suggests that its RNA transcript was activated by provirus integration in cis, possibly by the activity of a downstream provirus enhancer. Lactate dehydrogenase-elevating virus (LDV) can infect transplantable mouse tumors or xenograft tumors in mice through LDV-contaminated mouse biological materials, such as Matrigel, or through mice infected with LDV. These latter cell lines do express HLA-DR alpha-mRNA, as well as HLA-DR surface antigens. Furthermore, the tumorigenic CD44(+) cells differentially express the BMI1 gene, at both the RNA and protein levels. In contrast to cells in G1, cells cultured at 32.5 degrees C for prolonged periods during S phase and G2/M, and then returned to 37.5 degrees C, did not become committed to cell death.