Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.1.1.148 (Thy1)
 1,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Osteogenic cells were sorted from bone marrow of 5-fluorouracil (5-FU)-treated mice based on light scatter characteristics, Sca-1 expression, and their binding to wheat germ agglutinin (WGA). Four sort gates were established using forward (FSC) and perpendicular (SSC) light scatter and were denominated as FSChigh SSClow, FSClow SSChigh, FSClow SSClow, and FSChigh SSChigh cell. Cells from the FSChigh SSChigh gate, but not from the other gates, synthesized alkaline phosphatase, collagen, and osteocalcin and formed a mineralized matrix in culture. The number of osteoprogenitor cells was significantly enriched after depleting the 5-FU bone marrow from cells of the lymphoid and myeloid lineage, eg, T cells, B cells, natural killer cells, granulocytes, macrophages, and erythrocytes. Approximately 95% of the FSChigh SSChigh cell population of this "lineage-negative" (Lin-) marrow expressed the Sca-1 antigen (Sca-1+) and bound WGA. Three additional sort windows were established based on WGA binding intensity and were denominated as Sca-1+ WGAdull, Sca-1+ WGAmedium, and Sca-1+ WGAbright. Cells from the Sca-1+ WGAbright gate, but not from the other gates, synthesized bone proteins and formed a mineralized matrix. However, they lost this capacity upon subcultivation. Further immunophenotypic characterization showed that FSChigh SSChigh Lin- Sca-1+ WGAbright cells expressed stromal (KM16) and endothelial (Sab-1 and Sab-2) markers, but not hematopoietic surface markers such as c-kit and Thy1.2. Sorted FSChigh SSChigh Lin- Sca-1+ WGAbright cells form three-dimensional nodules that stain with the von Kossa technique and contain osteoblast and osteocyte-like cells.
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PMID:Characterization and purification of osteogenic cells from murine bone marrow by two-color cell sorting using anti-Sca-1 monoclonal antibody and wheat germ agglutinin. 751 72

A subset of mobilized CD34+ cells present in patient aphereses expresses Thy1 (CDw90). This population contains most long-term culture initiating cells, as assayed with a murine stromal cell line. It also contains a significant proportion of colony-forming unit granulocyte macrophage, but very few burst-forming unit erythroid. The limited differentiation towards the erythroid lineage is further confirmed by the absence of GATA-1 mRNA in the CD34+/Thy1+ subset, and by the low level of c-kit expression. The CD34+/Thy1+ subset appears phenotypically and functionally heterogeneous, a finding consistent with its high representation, compared to phenotypes such as CD34+/CD38-. Therefore, while at least some of CD34+/Thy1+ cells may be infectable by retroviral vectors, as shown by the presence of a transcript for the receptor for murine amphotropic retroviruses, the use of this selection strategy to specifically target human stem cells appears questionable.
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PMID:Phenotypic, molecular, and functional characterization of human peripheral blood CD34+/THY1+ cells. 856 66

Thymocytes of mice deficient in the recombinase-activating gene (RAG)-1 or RAG-2 cannot express and receive signals through the pre-TCR. As a result, thymocyte development in these mice terminates at the CD4/8 double negative (DN), IL-2R-alpha-positive stage. Nevertheless, RAG-deficient DN thymocytes express functional CD3 complexes and can therefore be induced by anti-CD3 epsilon mAb to mature to the CD4+8+ double positive stage. In the present paper we demonstrate that the peripheral lymphoid organs (lymph nodes, spleen) and peripheral blood of RAG-deficient mice harbor an immature T cell population which, similar to RAG-deficient DN thymocytes, contains high levels of cytoplasmic CD3 epsilon and responds to anti-CD3 epsilon mAb in vivo. With respect to surface phenotype (Thy1.2+, PgP-1+, HSA+, Fc gamma RII/III-, IL-2R-alpha-, c-kit-), these cells are similar to intermediate stage RAG-deficient DN thymocytes. Moreover, they express mRNA for pre-TCR-alpha and for the nondeleted RAG. Following injection of anti-CD3 epsilon mAb, these cells proliferate, down-regulate heat stable Ag and PgP-1, and partially differentiate to CD4+ and CD8+ double positive and single positive cells. The induced population displays a mixed phenotype, between that of immature thymocytes and lymph node T cells in normal mice. Induction is successful in thymectomized RAG-deficient mice, suggesting that it occurs in the periphery. However, after thymectomy, inducible cells disappear with an approximate half-life of 10 to 14 days. We suggest that DN thymocytes can emigrate and repopulate peripheral lymphoid organs of RAG-deficient mice. These cells respond to CD3 signaling by aberrant maturation, possibly due to the inappropriate microenvironment of peripheral lymphoid organs.
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PMID:Immature T cells in peripheral lymphoid organs of recombinase-activating gene-1/-2-deficient mice. Thymus dependence and responsiveness to anti-CD3 epsilon antibody. 856 35

A null cell line (SCM1) was established by a culture of spleen cells (SC) from normal adult C57B1/6 mice with complete medium alone for 10 days and followed by weekly cultures with a 25% WEHI-3 cell culture supernatant. Phenotype analysis showed that the SCM1 cells were negative for CD3, Thy1.2, B220, Mac-1, Gr-1, NK1.1 and MHC class II, but were positive for MHC class I, Fc gamma RII/ III, Fc epsilon RI, c-kit and the receptor against wheat germ agglutinin. These findings suggested that the SCM1 cells were mast cells. In an in vitro proliferation assay. SCM1 cells proliferated in the presence of either IL-3 or stem cell factor (SCF), but not in the presence of IL-4, whereas IL-4 showed an augmenting effect on their proliferation in the presence of either IL-3 or SCF. In analysing the mechanism by which such mast cells could be expanded from normal adult mouse SC, the addition of anti-IL-3 MoAb, but not anti-SCF MoAb, into the initial culture inhibited the subsequent expansion of either IL-3-or SCF-responding cells. The prior depletion of CD4+ T cells abrogated the capacity of the SC to enhance the expansion of SCF-responding cells, and this inability was restored by the addition of IL-3. Moreover, the culture supernatant of normal adult SC alone contained considerable levels of IL-3. Taken together, our findings suggest that, in an in vitro culture, CD4+ T cell-derived IL-3 therefore enhances the expansion of mast cells from the normal adult mouse spleen.
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PMID:IL-3 derived from CD4+ T cells is essential for the in vitro expansion of mast cells from the normal adult mouse spleen. 887 Jul 13

We have revealed that about one and a half thousand tiny clusters, filled with one thousand closely packed lymphocytes, can be found throughout the murine small and large intestinal mucosa. They are located in crypt lamina propria (cryptopatches; CP) and can be first detected at 14-17 d after birth. A large fraction of lymphocytes in CP expresses c-kit, IL-7R, Thy1 and a lymphocyte function-associated antigen, LFA-1, whereas most of them remain CD3-, TCR alpha beta-, TCR gamma delta-, sIgM-, and B220-. The population size of IL-2R alpha+, HSA+ and Pgp-1+ subsets is variable (20-50%) and the composition of CD8+, Ly-1+, and CD4+ subsets is smaller but also variable (3-20%). In the small intestine, CP do not contain cells undergoing apoptosis nor cells bearing RAG-1 molecules, but do contain dendritic stromal cells bearing CD11c/CD18 molecules. The frequency of DNA replicating cells in CP is higher than that in Peyer's patches (PP), is lower than that in the thymic cortex and is almost comparable with that in the thymic medulla. The numbers of CP remain the same in aged mice (> 114 wk) but double after estrogen treatment even though the thymi are attenuated sharply in both conditions. Thus, with respect to histogenesis, lymphocyte composition and tissue level of cellular behavior, neither PP, isolated lymphoid follicles, peripheral LNs, nor thymus are identical with CP. Finally, CP are virtually absent in lamina propria of IL-7R-deficient mice that display a profound reduction in thymic and peripheral lymphoid cellularity. By contrast, CP are present in germ-free mice and in athymic (nu/nu), SCID, TCR beta x delta-/-, RAG-2-/-, PP-deficient (aly/aly), stem cell factor (Sl/Sld) and c-kit (W/Wv) mutant mice. Taking all of these results together, CP are the first identification of gut-associated murine lymphoid tissues where the generation of IL-7-dependent lympho-hematopoietic progenitors for T and/or B cell descendants may start to take place at the age of commencement of weaning.
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PMID:Identification of novel lymphoid tissues in murine intestinal mucosa where clusters of c-kit+ IL-7R+ Thy1+ lympho-hemopoietic progenitors develop. 887 90

Osteoclasts are bone resorbing cells of hematopoietic origin; however, a progenitor cell population that gives rise to mature osteoclasts remains elusive. We have characterized a unique cell surface phenotype of clonogenic osteoclast progenitors (colony-forming unit-osteoclast [CFU-O]) and obtained a marrow cell population selectively enriched for these progenitors. Whole bone marrow cells were sequentially separated based on physical and cell surface characteristics, and the presence of CFU-O and other hematopoietic progenitors was examined. CFU-O was enriched in a nonadherent, low-density, lineage-marker-negative (Lin-), Thy1.2-negative (Thy1.2-), Sca1-negative (Sca1-), and c-kit-positive (c-kit+) population, as were the progenitors that were responsive to macrophage-colony-stimulating factor(CSF; CFU-M), granulocyte-macrophage-CSF (CFU-GM), and stem cell factor (CFU-SCF). When the Lin-Thy1.2-Sca1- population was divided into c-kithigh and c-kitlow populations based on c-kit fluorescence, over 88% of CFU-M, CFU-GM, and CFU-SCF were found in the c-kithigh population. In relation to the above mentioned hematopoietic progenitors, CFU-O was significantly higher in the c-kitlow population: 80% of progenitors present in the c-kitlow population were CFU-O. The CFU-O in both c-kithigh and c-kitlow populations showed key features of the osteoclast: multinucleated tartrate-resistant acid phosphatase-positive cell formation, expressions of vitronectin receptors, c-src and calcitonin receptors, and bone resorption. We have identified a progenitor cell population in the earliest stage of the osteoclast lineage so far described and developed a method to isolate it from other hematopoietic progenitors. This should help pave the way to understand the molecular mechanisms of osteoclast differentiation.
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PMID:Isolation and characterization of murine clonogenic osteoclast progenitors by cell surface phenotype analysis. 945 57

Fanconi anemia (FA) is a complex recessive genetic disease that causes bone marrow failure in children. The mechanism by which the gene for FA group C (Fancc) impinges on the normal hematopoietic program is unknown. Here we demonstrate that the bone marrow from Fancc-/- mice have reduced ability for primary and secondary long-term reconstitution of myeloablated recipients compared to wild-type or heterozygous mice, indicating that the Fancc gene product is required for the maintenance of normal numbers of hematopoietic stem cells. Long-term and secondary transplant studies suggested that there also were qualitative changes in their developmental potential. Consistent with the reduction in reconstitution, flow cytometric analysis of the primitive subfractions of hematopoietic cells obtained from the bone marrow of Fancc -/- mice demonstrated that they contained 40 to 70% fewer lineage-negative (Lin-)Thy1.2-/lowScal(+) c-Kit(+)CD34+ cells compared to controls. In contrast, the number of Lin Thy1.2-/ lowScal(+)c-Kit CD34(-)cells was comparable to that of wild-type mice. The differential behavior of Lin(-)Thy1.2-/lowScal+c-Kit+CD34+ and Lin(-)Thy1.2-/lowScal(+)c-Kit CD34 subfractions also was observed in mice treated with the DNA cross-linking agent mitomycin C(MMC). Fancc-/- mice treated with MMC had an 92% reduction of CD34 cells as compared to Fancc+/+ mice. The number of CD34 cells only was reduced about 20%. These results suggest that the Fancc gene may act at a stage of primitive hematopoietic cell development identified by CD34 expression.
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PMID:Hematopoietic compartment of Fanconi anemia group C null mice contains fewer lineage-negative CD34+ primitive hematopoietic cells and shows reduced reconstruction ability. 1056 Sep 14

Introduction of foreign genes into human CD34(+) hematopoietic precursor cells offers a means to correct inborn errors or to protect human stem cells from chemotherapeutic damage. Electroporation is a non-chemical, nonviral, highly reproducible means to introduce foreign genes into mammalian cells that has been used primarily for rapidly dividing cells. CD34(+) cells isolated from mobilized peripheral blood of patients were cultured for 48 h in serum-free culture medium supplemented with Flt-3 ligand, stem cell factor and thrombopoietin. Cell cycle analysis showed an increase in % S-phase from 2% on day 0 to 28% on day 2 without significant loss of mean fluorescence intensity (MFI). Optimal electroporation conditions for CD34(+) cells were 550 V/cm, 38 ms, 30 microg DNA/500 microl at cell densities between 0.2 x 10(6) and 10 x 10(6) cells/ml resulting in transient EGFP gene expression in 21% (+/- 1%) of CD34(+) precursor cells, as determined by flow cytometry 48 h after electroporation. The more primitive cells were also found to be EGFP(+) as determined by subset analysis using Thy1, CD38, AC133 and c-kit conjugated monoclonal antibodies. Methylcellulose assays on electroporated CD34(+) cells yielded 20% (+/- 7%) EGFP(+) colonies (CFU-GM, BFU-E and CFU-mix) and 22% (+/- 5%) EGFP(+) long-term colony-initiating cells (LTC-IC). The reporter gene was found to be integrated into the LTC-IC genomic DNA as determined by inverse PCR and DNA sequencing. These results suggest that electroporation has the potential to effectively and stably deliver exogenous genes into human hematopoietic precursor cells.
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PMID:Efficient expression of foreign genes in human CD34(+) hematopoietic precursor cells using electroporation. 1131 15

A transgenic reporter mouse strain, which expressed the human CD25 (hCD25) surface marker as a reporter under the control of the pre-T cell receptor alpha(pTalpha) promoter, was used to identify lymphoid precursors that expressed pTalpha intracellularly. The hCD25 reporter marked intra- and extrathymic precursors of lymphocytes but not myeloid cells. The earliest intrathymic precursors were CD4(lo)CD8(-)CD25(-)CD44(+)c-Kit(+) cells that expressed elevated levels of Notch-1 mRNA. Clonogenic assays showed that the extrathymic precursors were common lymphoid progenitors (CLPs) that included CD19(-), B220(+), Thy1(+) and CD4(+) cells. Thus, the pTalpha reporter can be used to trace lymphopoiesis between CLPs and alphabeta T cells. The slower extinction of the hCD25 reporter compared to pTalpha enabled us to define points at which pTalpha(-) lineages branched off.
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PMID:Tracing lymphopoiesis with the aid of a pTalpha-controlled reporter gene. 1192 10

Fanconi anemia (FA) is a complex recessive genetic disease characterized by progressive bone marrow (BM) failure. We have previously shown that stem cells from the FA group C mouse model have lower long-term primary and secondary reconstitution ability, and that bone marrow of Fancc(-/-) mice contained fewer lineage-negative (Lin(-))Thy1.2(low)Sca-1(+)c-kit(+) CD34(+) cells but normal levels of Lin(-)Thy1.2(low)Sca-1(+)c-kit(+)CD34(-) primitive cells. These data suggest that CD34(+) primitive cells have either a lower growth or differentiation potential, or that these cells have greater apoptosis levels. To investigate the role Fancc might have on the growth and differentiation potentials of primitive hematopoietic stem cells, we used a single-cell culture system and monitored cell viability, doubling potential, and apoptosis levels of Fancc(-/-) primitive Lin(-)Thy1.2(-)Sca-1(+) (LTS)-CD34(+) and LTS-CD34(-) stem cells. Results showed that Fancc(-/-) LTS-CD34(-) and LTS-CD34(+) cells had altered growth and apoptosis responses to combinations of stimulatory cytokines, most dramatically in response to a combination of factors that included interleukin-3 (IL-3) and IL-6. In addition, Fancc(-/-) LTS-CD34(-) and LTS-CD34(+) cells showed a lower differentiation potential than Fancc(+/+) cells. These results support a role for Fancc in the growth and differentiation of primitive hematopoietic cells and suggest that an altered response to stimulatory cytokines may contribute to BM aplasia in FA patients.
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PMID:Hematopoietic stem cells from fancc(-/-) mice have lower growth and differentiation potential in response to growth factors. 1235 14


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