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

The introduction of clonal assays and long-term culture systems has resulted in considerable progress in the understanding of the early events that control self-renewal and commitment to differentiation of pluripotent hematopoietic stem cells (PHSC). Relatively little is known about the factors that control the commitment of PHSC to the lymphoid lineages, especially the T cell lineage. In the present study, the expression of the proto-oncogene c-kit was used to isolate and study the capacity of highly purified day 14 colony-forming units-spleen (CFU-S) to reconstitute the thymus of sublethally irradiated Thy-1 congenic recipient mice. We demonstrate here that one c-kit positive (c-kitpos) stem cell upon intrathymic transfer can effectively reconstitute the thymus of a sublethally irradiated recipient. After a lag phase of 15 d, high levels of donor-derived thymocytes (Thy-1.1pos) could be detected until 65 d after transplantation in Thy-1.2pos host mice. Donor-derived cells were only detected in the lobe of the thymus in which cells were previously injected and not in the noninjected lobe. These data suggest that c-kitpos stem cells do not migrate from one lobe to another and that they do not re-seed the thymus after having migrated to the bone marrow. The level and duration of reconstitution was found to be cell dose dependent, suggesting that, over time, endogenous stem cells compete with donor stem cells for available sites in the thymus microenvironment. The data presented in this paper demonstrate that commitment of purified adult bone marrow-derived c-kitpos stem cells to the T cell differentiation pathway can occur in the thymus and does not have to happen in the bone marrow.
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PMID:Thymus reconstitution by c-kit-expressing hematopoietic stem cells purified from adult mouse bone marrow. 128 Dec 8

The interaction of the mouse c-kit receptor, designated Kit receptor, and steel factor promotes the proliferation and differentiation of hematopoietic progenitor cells. Monoclonal antibodies against the extracellular portion of the mouse Kit receptor were established. Five percent to 10% of total bone marrow cells expressed the Kit receptor, and half of them lack the expression of lineage markers. The Kit receptor was expressed on 70-80% of Thy-1.1lo Lin-Sca-1+ cells, which express Thy-1.1 antigen at a low level and constitute approximately 0.05% of adult bone marrow and fetal liver; by previous studies, these cells have been shown to be highly enriched for multipotent hematopoietic stem cells (HSCs) and are the only hematopoietic cell subset with this activity. Spleen colony formation and long-term multilineage reconstitution activities were contained in the Kit+ but not in the Kit- subpopulations of Thy-1lo Lin-Sca-1+ cells from adult bone marrow, suggesting that the Kit receptor is expressed on HSCs from the earliest stage-i.e., pluripotent HSCs. The role of steel factor in the development and self-renewal of HSCs was tested with Sl/Sl homozygote fetuses, which lack genes to encode functional steel factor. They were shown to have 30-40% of the number of HSCs on days 13-15 when compared with normal litermates. However, the absolute number of HSCs increased during fetal development in the Sl/Sl mice. The results suggest that the Kit receptor-steel factor interaction may not be essential for the initiation of hematopoiesis and the self-renewal of (at least) fetal HSCs.
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PMID:Evidence that hematopoietic stem cells express mouse c-kit but do not depend on steel factor for their generation. 137 59

To dissect mechanisms that co-ordinate specific events in thymopoiesis we have characterized alterations in thymic structure and function caused by expression of a transgene. This gene encodes SV40Tag and is specifically expressed in a subset of thymic epithelial (TE) cells around birth. As a result the number of immortal TE cells increases, thymic mass increases (up to 3 g), and thymopoiesis is expanded. The latter is reflected by a approximately 100-fold increase of the major thymocyte subsets and increased peripheral T cell counts. Grossly hyperplastic thymi retain many but not all morphological features of a normal thymus. Also in grafts, SV40Tag+ TE cells steer expansion (up to 8 g) and organize a tissue with mainly cortex-like features that includes mainly SV40Tag+ TE cells, thymocytes, and macrophages. To investigate expression of specialized gene functions in the immortal TE cells, a cell line was derived. The Epi-A1 cell line expresses the genes for major histocompatibility complex class I and II, Thy-1, interleukin (IL)-6, IL-7, macrophage-colony-stimulating factor, and transforming growth factor-beta 3. Most importantly, Epi-A1 cells also express the IL-4 receptor and the c-kit ligand (KL), a factor that, in concert with commitment factors, channels progenitors into hemopoietic lineages. The expression of low constitutive levels of KL mRNA does not require IL-4, but KL mRNA levels are increased dramatically in response to IL-4. Since constitutive expression of KL mRNA in vivo is restricted to a small subset of TE cells in the thymus, our findings reveal a novel specific interaction between thymocytes and a specialized subset of TE cells.
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PMID:Thymic hyperplasia in transgenic mice caused by immortal epithelial cells expressing c-kit ligand. 137 65

It was the objective of the study to characterize CD34+ hematopoietic progenitor cells from peripheral blood (PB) and bone marrow (BM) in a group of 24 cancer patients. After cytotoxic chemotherapy, R-metHu granulocyte colony-stimulating factor (R-metHuG-CSF; filgrastim, 300 micrograms daily, subcutaneously) was given to shorten the time of neutropenia as well as to increase the rebound of peripheral blood progenitor cells (PBPC) for harvesting. The proportion of CD34+ cells in the leukapheresis products (LPs) was 1.4-fold greater than in BM samples that were obtained at the same day (LP: median, 1.4% v BM: median, 1.0%, P < .01). Two- and three-color immunofluorescence showed that blood-derived CD34+ cells comprised a greater proportion of a particular early progenitor cell than CD34+ cells of bone marrow. Blood-derived progenitor cells tended to have a higher mean fluorescence intensity of CD34 and expressed significantly lower levels of HLA-DR (mean fluorescence intensity of HLA-DR: 442.6 +/- 44.9 [LP] v 661.5 +/- 64.6 [BM], mean +/- SEM, P < .01). Furthermore, the blood-derived CD34+ cells comprised a 1.7-fold greater proportion of Thy-1+ cells (LP: median, 24.4% v BM: median, 14.4%, P < .001) and expressed significantly less c-kit (LP: median, 20.5% v BM: median, 31.0%, P < .01). Three-color analysis showed that high levels of Thy-1 expression were restricted to CD34+/HLA-DRdim or CD34+/HLA-DR- cells confirming the early developmental stage of this progenitor cell subset. The proportion of CD34+/CD45RA(bright) cells representing late colony-forming unit granulocyte-macrophage (CFU-GM) was smaller in LPs compared with BM (P < .05). For an examination of BM CD34+ cells before the mobilization chemotherapy, samples of 16 patients were available. The mean proportion of c-kit expressing CD34+ cells in the bone marrow during G-CSF-stimulated reconstitution decreased 1.8-fold compared with baseline values. There was no difference in the proportion of BM-derived CD34+/Thy-1+ cells and CD34+/CD45RA+ cells between steady-state hematopoiesis and G-CSF-supported recovery. Our data suggest that during G-CSF-enhanced recovery, CD34+ cells in the PB are enriched with more primitive progenitor cells to evenly replenish the BM after the chemotherapy-related cytotoxic damage.
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PMID:Blood-derived autografts collected during granulocyte colony-stimulating factor-enhanced recovery are enriched with early Thy-1+ hematopoietic progenitor cells. 753 95

The early stages of lymphoid cell formation were studied by testing the differentiative potential of phenotypically defined subsets of CD34+ bone marrow cells. A subpopulation of CD34+ Lin- CD45RA+ cells expressing CD10 was isolated by flow cytometry. Such cells are CD38+, HLA-DR+, do not express significant levels of Thy-1 and c-kit, lack erythroid, myeloid, megakaryocytic potential, and give rise only to lymphoid T, B, natural killer (NK), and dendritic cells (DC) in kinetics and titration experiments. Limiting dilution analysis demonstrates the existence of multipotential B/NK/DC progenitor clones in the CD34hi Lin-CD10+ adult bone marrow cell population. Thus, nonprimitive progenitors for lymphoid cells and for DCs can be distinct from those of myeloid, megakaryocytic, and erythroid cells, implying that the DC lineage is developmentally more closely related to the lymphoid lineage than to the myeloid lineage. This study provides new insights into the organization and development of the human lympho-hematopoietic system.
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PMID:Human T, B, natural killer, and dendritic cells arise from a common bone marrow progenitor cell subset. 758 37

Expression of Thy-1 on hematopoietic cells from human fetal liver (FL), cord blood (CB), and bone marrow (BM) was studied with a novel anti-Thy-1 antibody, 5E10. Specificity of 5E10 for human Thy-1 was demonstrated by immunoprecipitation of a 25-35-kD molecule, and the sequence of a cDNA that was cloned by immunoselection of COS cells transfected with a cDNA library derived from a 5E10+ cell line. Two- and three-color immunofluorescence staining experiments revealed that the Thy-1 expression is restricted to, an average, 1-4% of FL, CB, and BM cells, and binding to these cell types is essentially restricted to a very small subset of lymphoid cells and approximately 25% of CD34+ cells. Thy-1+ CD34+ cells were further characterized as CD38lo/CD45RO+/CD45RA-/CD71lo/c-kit(lo) and rhodamine 123dull. When CD34+ cells were sorted on the basis of Thy-1 expression, the majority of clonogenic cells were recovered in the CD34+Thy-1- fraction, whereas the majority of cells capable of producing myeloid colonies after 5-8 wk of long-term culture (long-term culture initiating cells) were recovered in the Thy-1+CD34+ fraction. In addition to CD34+ cells, Thy-1 was found to be expressed on a variable, very small number (< 1%) of CD34- mononuclear cells in BM, CB, and peripheral blood that were further characterized as CD3+ CD4+ lymphocytes. The restricted expression of Thy-1 on primitive hematopoietic cells is in agreement with a previous report (Baum et al., 1992. Proc. Natl. Acad. Sci. USA. 89:2804) in which Thy-1 expression was used to enrich for primitive hematopoietic cells from fetal tissue. Compared with those previous studies, we found Thy-1 expression on a larger proportion of CD34+ cells (25% in our study vs. 5% in Baum et al.) and furthermore performed studies on Thy-1 expression on CD34+ cells from CB, FL, and BM in relation to markers that are known to be differentially expressed on hematopoietic cells. Taken together our results indicate that Thy-1-specific antibody 5E10 is an attractive tool for further studies on the biology and purification of human stem cells.
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PMID:Expression of Thy-1 on human hematopoietic progenitor cells. 768 34

The early thymus precursor population of adult mice has the capacity to generate T cells, B cells and dendritic cells (DC). These precursors were injected into the thymus of irradiated recipients in order to follow the kinetics of thymic DC development. The resultant cohort of T-lineage cells developing in the thymus was accompanied by a parallel cohort of DC, present at 10(3)-fold lower frequency. The intrathymic lifespan of these DC was as short as that of T-lineage thymocytes. As the thymic DC matured, some markers characteristic of the original precursor population gradually declined (Ly-5, c-kit, Sca-2) whereas markers characteristic of thymic DC appeared and were maintained (major histocompatibility complex class II, CD11c, NLDC-145 and CD8 alpha). Some thymic DC expressed the early B-cell marker BP-1, and BP-1 mRNA, throughout their maturation. The surface markers on thymic DC could be divided into two groups. Some markers, including class I and class II MHC, CD8 alpha and BP-1, appeared to be integral components of the DC surface. In contrast, other markers, including Thy-1, CD4 and CD8 beta, had probably been picked up from associated thymocytes.
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PMID:Mouse thymus dendritic cells: kinetics of development and changes in surface markers during maturation. 787 3

In the accompanying paper we showed that six distinct subsets of bone marrow (BM) cells can be identified using the mAb ER-MP12 and ER-MP20 in two-colour immunofluorescence analysis. Upon intrathymic transfer into sublethally irradiated mice thymus-repopulating ability was restricted to ER-MP20- BM cells expressing either high or intermediate levels of the ER-MP12 antigen (1-2% and approximately 30% of BM nucleated cells respectively). The highest frequency of thymus-repopulating cells was found in the minor subset of ER-MP12(+)+20- BM cells. In the present study we demonstrate that upon intravenous transfer, thymus-homing and -repopulating BM cells are exclusively confined to the ER-MP12(+)+20- and ER-MP12+20- subpopulations, the highest frequency being detected among ER-MP12(+)+20- BM cells. Analysis of the peripheral blood leucocytes of reconstituted mice showed that not only prothymocytes but also progenitor cells of the B cell lineage as well as the myeloid lineage were present within both subsets. Three-colour flow cytometric analysis revealed that ER-MP12(+)+20- BM cells in particular were phenotypically heterogeneous with respect to the expression of the cell surface markers Thy-1, Sca-1, CD44, B220 and c-kit. Taken together our data demonstrate that ER-MP12 positively identifies BM cells with the ability to home to and repopulate the thymus. The phenotypic heterogeneity displayed by the ER-MP12(+)+20- BM subset, containing the highest frequency of thymus-homing and -repopulating cells, provides a basis for further separation of prothymocyte activity from other haematopoietic activities in the BM of the mouse.
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PMID:ER-MP12 antigen, a new cell surface marker on mouse bone marrow cells with thymus-repopulating ability: II. Thymus-homing ability and phenotypic characterization of ER-MP12-positive bone marrow cells. 824 Oct 54

SL/Kh mice spontaneously develop pre-B lymphomas with surface phenotypes of B220+, BP-1+, Thy-1-, and surface immunoglobulin negative. The immunoglobulin heavy chain of lymphoma is clonally rearranged but the light chain gene remains in germline configuration. Studying prelymphoma stage SL/Kh bone marrow (BM), we found unusual multiclonal expansion of BP-1+ pre-B cells [34.8 +/- 5.8% (mean +/- SD)] by 4 weeks of age, whereas there were far fewer of such cells in most other laboratory strains (8 +/- 5%). The BP-1+ cells did not express surface immunoglobulin, Thy-1.1, or c-kit. Therefore, they seemed to belong to the pre-B II category. Increased numbers of BP-1+ cells were seen in F1 hybrids between SL/Kh and NFS/N; thus it was apparently a dominant heritable property of SL/Kh mice. Emergence of this population was independent of expression of endogenous ecotropic virus, since they were present in BMs of the F1 hybrid to C4W (Fv-4') and were not inhibited by neonatal injection of maternal resistance factor. In the radiation chimeras SL/Kh-->BALB/c, BP-1+ cells appeared abundantly (29.0 +/- 3.8%), whereas in the reciprocal chimeras BALB/c-->SL/Kh, for fewer (5.5 +/- 2.3%) appeared. Therefore, expansion of BP-1+ cells in prelymphomatous BM is a property of SL/Kh stem cells rather than BM microenvironments.
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PMID:Abnormal bone marrow B-cell differentiation in pre-B lymphoma-prone SL/Kh mice. 827 75

The SL/Kh strain of mice spontaneously develop two types of non-thymic lymphomas at a high incidence and very short latency. The major type of lymphomas induce systemic lymph node enlargement and hepatosplenomegaly, and the minor type, proliferation predominantly in bone marrow often associated with spinal paralysis. Phenotypes of both types of lymphomas are indistinguishable: they express B220, 6C3, c-kit but not Thy-1.1, Mac-1 and surface Ig. In both types of lymphomas, the immunoglobulin heavy chain gene is found clonally rearranged in the order of VH-D-JH, whereas the light chain gene remains in germ line configuration. About half of the primary lymphomas are dual or oligoclonal in origin. R-PCR also demonstrates expression of lambda 5, RAG-1 and RAG-2, which are specifically associated with pre-B stage lymphocytes. All these observations indicate that both types of the SL/Kh lymphomas are pre-B-lymphomas.
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PMID:SL/KH strain of mice: a model of spontaneous pre-B-lymphomas. 832 39


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