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Query: UNIPROT:P10721 (c-kit)
 6,575 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Athymic cytokine receptor gamma chain mutant mice that lack the thymus, Peyer's patches, cryptopatches (CP), and intestinal T cells were reconstituted with wild-type bone marrow cells. Bone marrow-derived TCR(-) intraepithelial lymphocytes (IEL) first appeared within villous epithelia of small intestine overlying the regenerated CP, and these TCR(-) IEL subsequently emerged throughout the epithelia. Thereafter, TCR(+) IEL increased to a comparable number to that in athymic mice and consisted of TCRgammadelta and TCRalphabeta IEL. In gut-associated lymphoid tissues of wild-type mice, only CP harbored a large population of c-kit(high)IL-7R(+)CD44(+)Thy-1(+/-)CD4(+/-)CD25(low/-)alpha(E) beta(7)(-)Lin(-) (Lin, lineage markers) lymphocytes that included cells expressing germline but not rearranged TCRgamma and TCRbeta gene transcripts. These findings provide direct evidence that gut CP develop progenitor T cells for extrathymic IEL descendants.
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PMID:Gut cryptopatches: direct evidence of extrathymic anatomical sites for intestinal T lymphopoiesis. 1111 81

Two types of T cells, alphabeta and gammadelta, develop in vertebrates. How these two T cell lineages arise from a common thymic T progenitor is poorly understood. Differentiation of alphabeta lineage T cells requires the surrogate alpha chain (pTalpha), which associates with the T cell receptor (TCR) beta chain to form the pre-TCR. gammadelta lineage development does not appear to involve an obligatory surrogate chain, but instead requires productive rearrangement and expression of both TCR gamma and delta genes. It has been proposed that the quality of signals transmitted by the pre-TCR and gammadelta TCR are distinct and that these "instructive" signals determine the lineage fate of an uncommitted progenitor cell. Here we show that the thymic T progenitor cells (CD25(+)CD44(+)c-kit(+)CD3(-)CD4(-)CD8(-) thymocytes, termed pro-T cells) from young adult mice that have yet to express TCRs can be subdivided based on interleukin 7 receptor (IL-7R) expression. These subsets exhibit differential potential to develop into gammadelta versus alphabeta lineage (CD4+CD8+ cells) in the thymus. Upon intrathymic injection, IL-7R(neg-lo) pro-T cells generated a 13-fold higher ratio of alphabeta lineage to gammadelta lineage cells than did IL-7R(+) pro-T cells. Much of this difference was due to a fivefold greater potential of IL-7R(+) pro-T cells to develop into TCR-gammadelta T cells. Evidence indicates that this biased developmental potential is not a result of enhanced TCR-gamma gene rearrangement/expression in IL-7R(+) pro-T cells. These results indicate that the pro-T cells are heterogeneous in developmental potential before TCR gene rearrangement and suggest that in some precursor cells the initial lineage commitment is independent of TCR-mediated signals.
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PMID:Evidence that gammadelta versus alphabeta T cell fate determination is initiated independently of T cell receptor signaling. 1125 36

In this study, the authors investigated normal cellular prion protein (PrP(C)) expression on murine immune systems using prion protein gene-deficient mouse as negative control. Immunocytes expressing PrP(C) in adult and fetal mice were detected by flow cytometry with the monoclonal antibody against PrP(C), 6H4. Cells from thymus and bone marrow reacted positively with 6H4, while spleen cells, peritoneal cells, peripheral blood leukocytes, and intestinal intraepithelial lymphocytes were nonreactive. In thymus, PrP(C) was observed in CD4(-)CD8(-) double-negative thymocytes. PrP(C+) cells of double-negative thymocytes belonged to the CD3(-) subset, but not to the CD3(+) subset. Triple-negative PrP(C+) thymocytes expressed CD44 or CD25 antigens. Furthermore, PrP(C) was observed in c-kit(+) bone marrow cells. In fetuses, PrP(C+) cells were observed in the liver and thymus at day 16.0 and 15.0 of gestation, respectively. These results demonstrated that PrP(C) is expressed on immature immunocytes.
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PMID:Distribution of cellular isoform of prion protein in T lymphocytes and bone marrow, analyzed by wild-type and prion protein gene-deficient mice. 1126 78

The earliest T cells homing to the thymus (CD3-CD4loCD8-) express CD117 (c-kit), CD43 (leukosialin), and the integrins CD11a (alphaL), CD11b (alphaM), CD29 (beta1), CD49f (alpha6), and CD44. Using reagents specific for CD44 variant isoforms (CD44v), we demonstrated that CD44v were expressed on virtually all early thymocytes,whereas cells carrying only the standard molecule (CD44s, not containing any variant domains), which is ubiquitously found on mature lymphocytes later, are very sparse. The expression of CD44v was closely correlated with CD43 and CD117 and was restricted to the CD3-CD4loCD8- stage. CD44v were detected on lymphocyte progenitor populations in the fetal blood, liver, thymus and spleen, as well as in the adult bone marrow. Functional studies demonstrated that only cells expressing CD44v from fetal liver and adult bone marrow could efficiently populate fetal thymic stroma and develop into mature T cells. In fetal thymic organ cultures anti-CD44v antibodies specifically blocked thymocyte development. We also present evidence that CD44v were required for the initial interaction of hematopoietic progenitor cells with the thymic stroma. Our data imply that CD44v are not only a useful marker for hematopoietic progenitors, but also play a functional role in the initiation of thymocyte development.
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PMID:Variant isoforms of CD44 are required in early thymocyte development. 1159 76

Although in vivo evidence supports a role for the murine intestinal epithelium in the extrathymic generation of certain intraepithelial T lymphocytes (IEL), no intraepithelial cells with in vitro lymphoid progenitor potential have yet been demonstrated. Using reaggregate fetal thymic organ culture techniques, we show that a subset of CD3(-) cells isolated from the intestinal epithelium of young mice is capable of generating T cells (alpha beta and gamma delta) and NK1.1(+) cells in vitro. A novel IEL subset bearing a low level of CD45 was identified and found to comprise cells expressing highly immature lymphoid markers including CD34, c-kit, CD122, CD127 and high levels of CD16 and CD44. This subset represents 20-30% of intraepithelial CD45(+) cells from 4-week-old wild-type and nude mouse strains and contains cells with in vitro T cell differentiation capacity. The identification of such an early pluripotent precursor phenotype within the intestinal epithelium implies that the potential for T cell generation exists at this site, and suggests that extrathymic T cell generation may occur within the epithelium itself.
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PMID:Identification and characterization of lymphoid precursors in the murine intestinal epithelium. 1174 50

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

C3H/He mice produce myeloid leukemias after whole body irradiation of 1-3Gy as compared with non-irradiated controls that produce fewer than 1% of leukemia [Radiatiton Research 127 (1991) 146]. Thus, p53-deficient C57BL/6 strain, a malignant lymphoma prone, was crossed back into C3H/He strain. Lethally irradiated wild-type mice to which p53-deficient bone marrow cells were transplanted (transplantation assay) showed dramatic change in the propensity of leukemia of myeloid lineages, the cells lacking CD3, Thy1.2, sIgM, B220, Mac-1, Gr-1, but being positive for c-Kit and CD44. Furthermore, transplanted mice subjected to 3Gy irradiation gave rise to a faster development of leukemia and a higher frequency of double-lineage leukemias than the non-irradiated control.
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PMID:Stem-cell leukemia: p53 deficiency mediated suppression of leukemic differentiation in C3H/He myeloid leukemia. 1244 80

Recombination-activating gene (RAG) 1 and 2 are essential for the gene rearrangement of antigen receptors of both T and B cells. To investigate RAG gene expression in peripheral lymphoid organs other than the thymus and bone marrow, we established mice in which a green fluorescent protein (GFP) gene is knocked-in the RAG2 gene locus (RAG2-GFP mice). In the thymus and bone marrow of heterozygous RAG2-GFP mice, as expected, GFP expression was detected in the appropriate stages of developing T and B cells. Interestingly, only a fraction of Thy-1.2(+) cells in the Peyer's patch were found to be GFP(+) amongst the peripheral lymphoid organs. The GFP(+) cells expressed high levels of surface TCRbeta and CD3, suggesting mature T cells with rearranged TCRalphabeta. However, they showed activated/memory phenotypes, i.e. CD45RB(low), CD69(high), CD44(high) and CD62L(low), and belonged to a CD4(+)CD8(+) population expressing c-kit, IL-7R and pTalpha characteristic of immature developing lymphocytes. Moreover, RAG(+) Peyer's patch T cells seem to be of thymic origin as judged by their expression of CD8alphabeta. These results show that there exists a fraction of mature T cells expressing RAG genes in the Peyer's patch, implying a potential for a secondary rearrangement of TCR in extrathymic tissues.
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PMID:Expression of recombination-activating gene in mature peripheral T cells in Peyer's patch. 1261 83

Bone marrow contains a population of rare progenitor cells capable of differentiating into osteoblasts, chondrocytes, adipocytes, myoblasts, and hematopoiesis-supporting stromal cells. These cells, referred to as mesenchymal progenitor cells (MPCs), can be purified and culture-expanded from animals and humans. Using bone-marrow-conditioned medium combined with basic fibroblast growth factor, we cultured a relatively homogeneous population of MPCs from murine bone marrow, which uniformly expressed stem cell antigen-1, CD29, CD44, c-kit, and CD105, while being negative for expression of CD45, CD31, and CD34. In vitro differentiation assays showed the tripotential differentiation capacities of these cells toward adipogenic, osteogenic, and chondrogenic lineages. Most importantly, immunophenotypic analyses demonstrated that MPCs did not express major histocompatibility complex class II molecules or the T-cell costimulatory molecules CD80 and CD86, consistent with further investigation showing that MPCs failed to elicit a proliferative response from allogeneic lymphocytes. Moreover, when allogeneic or third-party MPCs were added to T cells stimulated by allogeneic lymphocytes or the potent T-cell mitogen concanavalin-A, a significant reduction in T-cell proliferation was observed. In conclusion, our data demonstrate that we successfully isolated and culture-expanded a relatively homogeneous population of MPCs from adult murine bone marrow. Additionally, these primary cells could suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. This immunoregulatory feature of MPCs strongly implies that they may have potential applications in allograft transplantation.
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PMID:Isolation of mouse marrow mesenchymal progenitors by a novel and reliable method. 1296 7

Human mesenchymal stem cells (MSC), that have been reported to be present in bone marrow, adipose tissues, dermis, muscles and peripheral blood, have the potential to differentiate along different lineages including those forming bone, cartilage, fat, muscle and neuron. This differentiation potential makes MSC excellent candidates for cell-based tissue engineering. In this study, we have examined phenotypes and gene expression profile of the human adipose tissue-derived stromal cells (ATSC) in the undifferentiated states, and compared with that of bone marrow stromal cells (BMSC). ATSC were enzymatically released from adipose tissues from adult human donors and were expanded in monolayer with serial passages at confluence. BMSC were harvested from the metaphysis of adult human femur. Flowcytometric analysis showed that ATSC have a marker expression that is similar to that of BMSC. ATSC expressed CD29, CD44, CD90, CD105 and were absent for HLA-DR and c-kit expression. Under appropriate culture conditions, MSC were induced to differentiate to the osteoblast, adipocyte, and chondrogenic lineages. ATSC were superior to BMSC in respect to maintenance of proliferating ability, and microarray analysis of gene expression revealed differentially expressed genes between ATSC and BMSC. The proliferating ability and differentiation potential of ATSC were variable according to the culture condition. The similarities of the phenotypes and the gene expression profiles between ATSC and BMSC could have broad implications for human tissue engineering.
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PMID:Characterization and expression analysis of mesenchymal stem cells from human bone marrow and adipose tissue. 1531 35


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