The Experts below are selected from a list of 312 Experts worldwide ranked by ideXlab platform
Irving L Weissman - One of the best experts on this subject based on the ideXlab platform.
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hematopoietic stem Cell self renewal versus differentiation
Wiley Interdisciplinary Reviews: Systems Biology and Medicine, 2010Co-Authors: Jun Seita, Irving L WeissmanAbstract:: The mammalian blood system, containing more than 10 distinct Mature Cell types, stands on one specific Cell type, hematopoietic stem Cell (HSC). Within the system, only HSCs possess the ability of both multipotency and self-renewal. Multipotency is the ability to differentiate into all functional blood Cells. Self-renewal is the ability to give rise to HSC itself without differentiation. Since Mature blood Cells (MBCs) are predominantly short-lived, HSCs continuously provide more differentiated progenitors while properly maintaining the HSC pool size throughout life by precisely balancing self-renewal and differentiation. Thus, understanding the mechanisms of self-renewal and differentiation of HSC has been a central issue. In this review, we focus on the hierarchical structure of the hematopoietic system, the current understanding of microenvironment and molecular cues regulating self-renewal and differentiation of adult HSCs, and the currently emerging systems approaches to understand HSC biology.
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enforced bcl 2 expression overrides serum and feeder Cell requirements for mouse embryonic stem Cell self renewal
Proceedings of the National Academy of Sciences of the United States of America, 2005Co-Authors: Toshiyuki Yamane, Scott J Dylla, Manja Muijtjens, Irving L WeissmanAbstract:Leukemia inhibitory factor (LIF) is required, but not sufficient, for pluripotent mouse embryonic stem (ES) Cell expansion in vitro in the absence of serum or a feeder Cell layer, suggesting that additional signals are provided by serum or feeders that are necessary to support self-renewal. Here we show that transgenic ES Cell lines expressing Bcl-2, an antiapoptotic protein, continue to self-renew in serum- and feeder-free conditions when supplemented with LIF; even in the absence of bone morphogenic proteins. Bcl-2-expressing clones sustain the characteristics of undifferentiated, pluripotent ES Cells during long-term culture, and maintain their potential to differentiate into Mature Cell types. These results suggest that LIF and Bcl-2 overexpression are sufficient to expand these mouse pluripotent stem Cells in vitro.
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translating stem and progenitor Cell biology to the clinic barriers and opportunities
Science, 2000Co-Authors: Irving L WeissmanAbstract:Stem Cells are the natural units of embryonic generation, and also adult regeneration, of a variety of tissues. Recently, the list of tissues that use the model of differentiation from stem to progenitor to Mature Cell has increased from blood to include a variety of tissues, including both central and peripheral nervous systems and skeletal muscle; it is also possible that all organs and tissues are derived from, and still contain, stem Cells. Because the number and activities of stem Cells and their progeny are homeostatically regulated, clinical stem Cell transplantation could greatly add to the physician's armamentarium against degenerative diseases.
Mitsuo Honda - One of the best experts on this subject based on the ideXlab platform.
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Soluble interleukin-6 receptor is released from receptor-bearing Cell lines in vitro.
Japanese Journal of Cancer Research, 1992Co-Authors: Toshiharu Nakajima, Toshio Hirano, Tadamitsu Kishimoto, Kiyoshi Yasukawa, Tohru Tokunaga, Shinji Yamamoto, Ming Cheng, Mitsuo HondaAbstract:Soluble interleukin-6 receptor (sIL-6R) was found to be spontaneously released from human myeloma Cell line U266 Cells into culture supernatant, and was quantitatively measured with a fluorescence sandwich enzyme-linked immunosorbent assay employing antibodies specific to IL-6R. The supernatant IL-6R was generated only from IL-6R-positive Cell lines; myeloma Cell lines RPMI8226 and RPMI1788, and myelomonocytic Cell lines U937, THP-1, and HL-60. In contrast, it was not released from the IL-6R-negative Cells; T Cell line MoIt-4 and Burkitt lympboma Cell line Raji. SDS-PAGE analysis of the soluble IL-6R from U266 Cells suggested a molecular weight of approximately 50-55 kDa, 25–30 kDa smaller than the Mature Cell surface receptor. These results suggest that the generation of soluble IL-6R may be a maker of myeloma Cells and myelomonocytic Cells.
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Soluble Interleukin‐6 Receptor Is Released from Receptor‐bearing Cell Lines in vitro
Japanese Journal of Cancer Research, 1992Co-Authors: Toshiharu Nakajima, Toshio Hirano, Tadamitsu Kishimoto, Kiyoshi Yasukawa, Tohru Tokunaga, Shinji Yamamoto, Ming Cheng, Mitsuo HondaAbstract:Soluble interleukin-6 receptor (sIL-6R) was found to be spontaneously released from human myeloma Cell line U266 Cells into culture supernatant, and was quantitatively measured with a fluorescence sandwich enzyme-linked immunosorbent assay employing antibodies specific to IL-6R. The supernatant IL-6R was generated only from IL-6R-positive Cell lines; myeloma Cell lines RPMI8226 and RPMI1788, and myelomonocytic Cell lines U937, THP-1, and HL-60. In contrast, it was not released from the IL-6R-negative Cells; T Cell line MoIt-4 and Burkitt lympboma Cell line Raji. SDS-PAGE analysis of the soluble IL-6R from U266 Cells suggested a molecular weight of approximately 50-55 kDa, 25–30 kDa smaller than the Mature Cell surface receptor. These results suggest that the generation of soluble IL-6R may be a maker of myeloma Cells and myelomonocytic Cells.
Hal E Broxmeyer - One of the best experts on this subject based on the ideXlab platform.
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implications of dpp4 modification of proteins that regulate stem progenitor and more Mature Cell types
Blood, 2013Co-Authors: Xuan Ou, Heather Oleary, Hal E BroxmeyerAbstract:Dipeptidylpeptidase (DPP) 4 has the potential to truncate proteins with a penultimate alanine, proline, or other selective amino acids at the N-terminus. DPP4 truncation of certain chemokines, colony-stimulating factors, and interleukins have recently been linked to regulation of hematopoietic stem/progenitor Cells, more Mature blood Cells, and other Cell types. We believe that the potential role of DPP4 in modification of many regulatory proteins, and their subsequent effects on numerous stem/progenitor and other Cell-type functions has not been adequately appreciated. This review addresses the potential implications of the modifying effects of DPP4 on a large number of cytokines and other growth-regulating factors with either proven or putative DPP4 truncation sites on hematopoietic Cells, and subsequent effects of DPP4-truncated proteins on multiple aspects of steady-state and stressed hematopoiesis, including stem/progenitor Cell, and more Mature Cell, function.
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Implications of DPP4 modification of proteins that regulate stem/progenitor and more Mature Cell types.
Blood, 2013Co-Authors: Xuan Ou, Heather O'leary, Hal E BroxmeyerAbstract:Dipeptidylpeptidase (DPP) 4 has the potential to truncate proteins with a penultimate alanine, proline, or other selective amino acids at the N-terminus. DPP4 truncation of certain chemokines, colony-stimulating factors, and interleukins have recently been linked to regulation of hematopoietic stem/progenitor Cells, more Mature blood Cells, and other Cell types. We believe that the potential role of DPP4 in modification of many regulatory proteins, and their subsequent effects on numerous stem/progenitor and other Cell-type functions has not been adequately appreciated. This review addresses the potential implications of the modifying effects of DPP4 on a large number of cytokines and other growth-regulating factors with either proven or putative DPP4 truncation sites on hematopoietic Cells, and subsequent effects of DPP4-truncated proteins on multiple aspects of steady-state and stressed hematopoiesis, including stem/progenitor Cell, and more Mature Cell, function.
Olaf Schneewind - One of the best experts on this subject based on the ideXlab platform.
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anchoring of surface proteins to the Cell wall of staphylococcus aureus iii lipid ii is an in vivo peptidoglycan substrate for sortase catalyzed surface protein anchoring
Journal of Biological Chemistry, 2002Co-Authors: Adrienne M Perry, Hung Tonthat, Sarkis K Mazmanian, Olaf SchneewindAbstract:Surface proteins of Staphylococcus aureus are anchored to the Cell wall peptidoglycan by a mechanism requiring a C-terminal sorting signal with an LPXTG motif. Surface proteins are first synthesized in the bacterial cytoplasm and then transported across the cytoplasmic membrane. Cleavage of the N-terminal signal peptide of the cytoplasmic surface protein P1 precursor generates the extraCellular P2 species, which is the substrate for the Cell wall anchoring reaction. Sortase, a membrane-anchored transpeptidase, cleaves P2 between the threonine (T) and the glycine (G) of the LPXTG motif and catalyzes the formation of an amide bond between the carboxyl group of threonine and the amino group of Cell wall cross-bridges. We have used metabolic labeling of staphylococcal cultures with [32P]phosphoric acid to reveal a P3 intermediate. The 32P-label of immunoprecipitated surface protein is removed by treatment with lysostaphin, a glycyl-glycine endopeptidase that separates the Cell wall anchor structure. Furthermore, the appearance of P3 is prevented in the absence of sortase or by the inhibition of Cell wall synthesis. 32P-Labeled Cell wall anchor species bind to nisin, an antibiotic that is known to form a complex with lipid II. Thus, it appears that the P3 intermediate represents surface protein linked to the lipid II peptidoglycan precursor. The data support a model whereby lipid II-linked polypeptides are incorporated into the growing peptidoglycan via the transpeptidation and transglycosylation reactions of Cell wall synthesis, generating Mature Cell wall-linked surface protein.
Toshiharu Nakajima - One of the best experts on this subject based on the ideXlab platform.
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Soluble interleukin-6 receptor is released from receptor-bearing Cell lines in vitro.
Japanese Journal of Cancer Research, 1992Co-Authors: Toshiharu Nakajima, Toshio Hirano, Tadamitsu Kishimoto, Kiyoshi Yasukawa, Tohru Tokunaga, Shinji Yamamoto, Ming Cheng, Mitsuo HondaAbstract:Soluble interleukin-6 receptor (sIL-6R) was found to be spontaneously released from human myeloma Cell line U266 Cells into culture supernatant, and was quantitatively measured with a fluorescence sandwich enzyme-linked immunosorbent assay employing antibodies specific to IL-6R. The supernatant IL-6R was generated only from IL-6R-positive Cell lines; myeloma Cell lines RPMI8226 and RPMI1788, and myelomonocytic Cell lines U937, THP-1, and HL-60. In contrast, it was not released from the IL-6R-negative Cells; T Cell line MoIt-4 and Burkitt lympboma Cell line Raji. SDS-PAGE analysis of the soluble IL-6R from U266 Cells suggested a molecular weight of approximately 50-55 kDa, 25–30 kDa smaller than the Mature Cell surface receptor. These results suggest that the generation of soluble IL-6R may be a maker of myeloma Cells and myelomonocytic Cells.
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Soluble Interleukin‐6 Receptor Is Released from Receptor‐bearing Cell Lines in vitro
Japanese Journal of Cancer Research, 1992Co-Authors: Toshiharu Nakajima, Toshio Hirano, Tadamitsu Kishimoto, Kiyoshi Yasukawa, Tohru Tokunaga, Shinji Yamamoto, Ming Cheng, Mitsuo HondaAbstract:Soluble interleukin-6 receptor (sIL-6R) was found to be spontaneously released from human myeloma Cell line U266 Cells into culture supernatant, and was quantitatively measured with a fluorescence sandwich enzyme-linked immunosorbent assay employing antibodies specific to IL-6R. The supernatant IL-6R was generated only from IL-6R-positive Cell lines; myeloma Cell lines RPMI8226 and RPMI1788, and myelomonocytic Cell lines U937, THP-1, and HL-60. In contrast, it was not released from the IL-6R-negative Cells; T Cell line MoIt-4 and Burkitt lympboma Cell line Raji. SDS-PAGE analysis of the soluble IL-6R from U266 Cells suggested a molecular weight of approximately 50-55 kDa, 25–30 kDa smaller than the Mature Cell surface receptor. These results suggest that the generation of soluble IL-6R may be a maker of myeloma Cells and myelomonocytic Cells.