Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P10721 (c-kit)
 6,575 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have identified a population of cells in murine bone marrow that has many of the phenotypic characteristics attributed to resting hematopoietic stem cells but does not reconstitute irradiated mice. These cells express high levels of Sca-1, H-2K and CD38 and low levels of Thy-1.1, but do not express CD34 nor any of the lineage markers including CD3, CD4, CD5, CD8 NK1.1, I-A, B220, Ig(MGA), CD40, kappa, Mac-1, Gr-1 or Ter119. In addition, this population can be found at normal frequency in nu/nu as well as rag-1-/- mice. These cells incorporate only low levels of Rh123, are resistant to the cytotoxic effects of 5-fluorouracil and, consistent with their resting phenotype, less than 2% of these cells are in the S/G2/M phases of the cell cycle. The only phenotypic characteristic that distinguishes these cells from the lineage- Sca-1+, Thy-1.1low long-term reconstituting hematopoietic stem cell population is their lack of c-kit expression. Here we have explored the possibility that these cells represent a truly resting population of hematopoietic stem cells. We found that the lineage-, Sca-1+, c-kit- cells do not respond to hematopoietic growth factors in vitro, either alone or in combination with stromal layers. Furthermore, these cells do not form in vivo spleen colonies nor do they have the ability to reconstitute irradiated mice. Thus, this population may represent either a population of resting stem cells for which we lack the appropriate activating stimulus, or simply represent a "mystery population" that phenotypically mimics most of the physical properties of resting stem cells. Given the close phenotypic similarity of the c-kit- mystery population cells to the c-kit+ long-term reconstituting stem cells, investigators must be rigorous to exclude their effects from other stem cell assays.
 ...
PMID:Characterization of a population of cells in the bone marrow that phenotypically mimics hematopoietic stem cells: resting stem cells or mystery population? 947 46

CD45-negative B-cell precursor acute lymphoblastic leukaemia (ALL) provides a unique model to study the stem cell compartment in ALL as leukaemic CD34-positive cells, unlike their normal counterparts, do not express CD45. By increasing the number of events analysed to 10(6), storing only the events in the region of interest (storage gate), using appropriate isotype controls and stringent washing procedures, a flow cytometric protocol was established to characterize rare CD34+ CD19- events. In eight of 12 patients (67%) with CD45-negative B-cell precursor ALL, a distinct CD34+ CD19- CD45+ candidate normal stem cell population could be detected. In one patient analysed by four-colour staining, the CD34+ CD19- CD45+ cells, unlike the CD45-negative leukaemic cells, expressed CD117 (c-kit), providing further evidence that these cells represent residual nonleukaemic normal cells. By multiparameter analysis, this population of candidate normal stem cells could be separated from contaminating leukaemic CD34+ CD19- CD45- cells, which were detected in 11 of the 12 patients within the CD34+ CD19- compartment.
 ...
PMID:Flow cytometric identification of candidate normal stem cell populations in CD45-negative B-cell precursor acute lymphoblastic leukaemia. 950 32

Totipotent murine ES cells have an enormous potential for the study of cell specification. Here we demonstrate that ES cells can differentiate to hemopoietic cells through the proximal lateral mesoderm, merely upon culturing in type IV collagen-coated dishes. Separation of the Flk1+ mesoderm from other cell lineages was critical for hemopoietic cell differentiation, whereas formation of the embryoid body was not. Since the two-dimensionally spreading cells can be monitored easily in real time, this culture system will greatly facilitate the study of the mechanisms involved in the cell specification to mesoderm, endothelial, and hemopoietic cells. In the culture of ES cells, however, lineages and stages of differentiating cells can only be defined by their own characteristics. We showed that a combination of monoclonal antibodies against E-cadherin, Flk1/KDR, PDGF receptor(alpha), VE-cadherin, CD45 and Ter119 was sufficient to define most intermediate stages during differentiation of ES cells to blood cells. Using this culture system and surface markers, we determined the following order for blood cell differentiation: ES cell (E-cadherin+Flk1-PDGFRalpha-), proximal lateral mesoderm (E-cadherin-Flk1+VE-cadherin-), progenitor with hemoangiogenic potential (Flk1+VE-cadherin+CD45-), hemopoietic progenitor (CD45+c-Kit+) and mature blood cells (c-Kit-CD45+ or Ter119+), though direct differentiation of blood cells from the Flk1+VE-cadherin- stage cannot be ruled out. Not only the VE-cadherin+CD45- population generated from ES cells but also those directly sorted from the yolk sac of 9.5 dpc embryos have a potential to give rise to hemopoietic cells. Progenitors with hemoangiogenic potential were identified in both the Flk1+VE-cadherin- and Flk1+VE-cadherin+ populations by the single cell deposition experiment. This line of evidence implicates Flk1+VE-cadherin+ cells as a diverging point of hemopoietic and endothelial cell lineages.
 ...
PMID:Progressive lineage analysis by cell sorting and culture identifies FLK1+VE-cadherin+ cells at a diverging point of endothelial and hemopoietic lineages. 952 12

An autopsy case of systemic mast cell disease (SMCD) without primary skin lesions in a 57-year-old Japanese male is described. Initially the patient was suspected of having liver cirrhosis or malignant lymphoma because of hepatomegaly and lymph node enlargement on admission. However, a lymph node biopsy and bone marrow aspiration conducted on his third admission indicated a SMCD because of the existence of metachromatic cell aggregates stained with toluidine blue. At autopsy, the diagnosis was confirmed because the proliferating cells were histochemically proven to be mast cells by naphthol AS.D chloroacetate esterase, Giemsa and alcian blue, in addition to toluidine blue staining. The intra-abdominal and retroperitoneal lymph nodes were replaced by mast cell aggregates, which caused the splenic infarction and bilateral hydronephrosis, with infiltration of mast cells into the spleen and kidneys also being apparent. Mast cell infiltration was similarly found in the bone marrow, liver, ileum and ascending colon. Immunohistochemically, the mast cells were positive for antibodies of alpha 1-antichymotrypsin, CD45 (LCA), CD43 (MT-1), CD45R (MB-1) and the oncoprotein c-kit. Electron microscopic examination using formalin-fixed tissue gave supportive evidence of a mast cell origin for the lesions.
 ...
PMID:Systemic mast cell disease with splenic infarction: a case report. 970 48

Mast cells (MC) are important cellular components of the immune network in diverse organs. The skin MC has likewise been implicated in IgE- and complement-mediated cutaneous reactions. Such reactions supposedly involve specific cell surface membrane receptors. In this study, the cell surface marker profile of human skin MC was established using monoclonal antibodies (MoAb) against defined CD antigens. MC were isolated from juvenile foreskin (n = 55) and adult mammary skin (n = 5). The reactivity of MC with MoAb was assessed by a combined toluidine blue/immunofluorescence staining technique. Confirming our previous analyses on lung MC, foreskin MC reacted with MoAb against CD9, CD29, CD33, CD43, CD44, CD45, CD46, CD51, CD54, CD55, CD58, CD59, CD61, and CD117 (c-kit). Foreskin MC were also recognized by MoAb to CD47, CD48, CD49d, CD53, CD60, CD63, CD81, CD82, CD84, CD87, CD92, CD97, CD98, and CD99. Recently clustered CD antigens detectable on foreskin MC were CD147 (neurothelin), CD149 (MEM133), CD151 (PETA-3), and CD157 (BST-1). In contrast to lung MC and MC from adult skin, foreskin MC were found to express CD88 (C5aR). Also, cutaneous MC (from both juvenile foreskin and adult mammary skin), but not lung MC, were found to bind the CD32 MoAb IV.3, 2E1, and FLI8.26 (Fc gammaRII). The CD50 antigen (ICAM-3) was detectable on lung MC, but not on foreskin MC or MC of adult mammary skin. In summary, our data show that cutaneous MC and lung MC express an almost identical phenotype; however, in contrast to lung MC, cutaneous MC appear to express substantial amounts of CD32 and to lack CD50. In addition, foreskin MC, unlike MC from adult skin or lung, express CD88.
 ...
PMID:Phenotypic characterization of human skin mast cells by combined staining with toluidine blue and CD antibodies. 976 55

It is now accepted from studies in animal models that hematopoietic stem cells emerge in the para-aortic mesoderm-derived aorta-gonad-mesonephros region of the vertebrate embryo. We have previously identified the equivalent primitive hematogenous territory in the 4- to 6-week human embryo, under the form of CD34(+)CD45(+)Lin- high proliferative potential hematopoietic cells clustered on the ventral endothelium of the aorta. To characterize molecules involved in initial stem cell emergence, we first investigated the expression in that territory of known early hematopoietic regulators. We herein show that aorta-associated CD34(+) cells coexpress the tal-1/SCL, c-myb, GATA-2, GATA-3, c-kit, and flk-1/KDR genes, as do embryonic and fetal hematopoietic progenitors later present in the liver and bone marrow. Next, CD34(+)CD45(+) aorta-associated cells were sorted by flow cytometry from a 5-week embryo and a cDNA library was constructed therefrom. Differential screening of that library with total cDNA probes obtained from CD34(+) embryonic liver cells allowed the isolation of a kinase-related sequence previously identified in KG-1 cells. In addition to emerging blood stem cells, KG-1 kinase is also strikingly expressed in all developing endothelial cells in the yolk sac and embryo, which suggests its involvement in the genesis of both hematopoietic and vascular cell lineages in humans.
 ...
PMID:Molecular identity of hematopoietic precursor cells emerging in the human embryo. 980 56

Stem cells first enter the thymus around the 11th to 12th days of gestation in BALB/c mouse embryos. The phenotype of these stem cells has been difficult to determine because their entry occurs when the thymic primordium is very small and involves too few stem cells to allow studies by flow cytometry. We have been able to microdissect the thymus from embryos during this stage and immunophenotype cells in sections using a sensitive tyramide amplification system. Our results show that migrant stem cells express CD45, c-kit, CD44, CD34 and alpha4 integrin, but other markers such as CD62L, CD25, Thy-1.2, CD3epsilon, alpha5 integrin and RAG-1 expression are detected only after stem cell entry. These results should help to improve the isolation and characterization of migrant thymic stem cells.
 ...
PMID:Studies on the phenotype of migrant thymic stem cells. 993 88

We previously reported that the mouse GATA-2 gene is regulated by two alternative promoters (Minegishi et al, J Biol Chem, 273:3625, 1998). Although the more proximal IG (general) promoter is active in almost all GATA-2-expressing cells, the distal IS (specific) promoter activity was selectively detected in hematopoietic tissues but not in other mesodermal tissues. We report here in vivo analysis of the GATA-2 locus and its regulatory characteristics in hematopoietic tissues of transgenic mice. Transgenes containing 6 or 7 kbp of sequence flanking the 5' end of the IS first exon direct expression of beta-galactosidase or green fluorescent protein (GFP) reporter genes specifically to the para-aortic splanchnopleura, aorta-gonads, and mesonephros (AGM) region, and in the neural tissues. In situ hybridization analysis showed that reporter gene expression specifically recapitulates the endogenous expression profile of GATA-2 in these tissues. The flk-1, CD34, c-kit, and CD45 antigens were identified in the GFP-positive cells from the AGM region and fetal liver, indicating that GATA-2 is expressed in immature hematopoietic cells. Deletion of 3.5 kbp from the 5' end of the 6.0 kbp IS promoter construct, including one of the DNase I hypersensitive sites, completely abolished hematopoietic expression. These experiments describe an early developmental GATA-2 hematopoietic enhancer located between 6.0 and 2.5 kbp 5' to the IS exon.
 ...
PMID:The mouse GATA-2 gene is expressed in the para-aortic splanchnopleura and aorta-gonads and mesonephros region. 1036 Nov 17

A novel primitive hematopoietic cell line, THS119, was established from lineage marker negative (Lin-)/Sca-1+ cells from bone marrow of temperature-sensitive (ts) SV40 T-antigen transgenic mice after lengthy passaging by coculture with TBR59 bone marrow stromal cells. THS119 cells exhibited immature primitive hematopoietic cells such as forming cobblestones underneath the stromal cell layers. They retained properties of hematopoietic stem cells as shown by expression of c-Kit, Sca-1 and CD34low, but lacked hematopoietic lineage surface markers of differentiated hematopoietic cells (Gr-1, TER119, Mac-1, CD3, B220). RT-PCR analysis showed that THS119 cells exhibited multiple expression of both earlier developmental markers of myeloid, lymphoid and the hematopoietic cell specific transcription factors. THS119 cells showed temperature-dependent growth reflecting ts T-antigen, and their maintenance was TBR59 stromal cell-dependent. The requirement of stromal cells could not be replaced by cytokines, however, an IL-3 or IL-7 dependent cell line was generated after prolonged culture of THS119 cells on the stromal cells in the presence of these cytokines, and these cytokine-dependent cell lines exhibited phenotypes similar to the parental cells in their gene expression. SCF/c-Kit interaction is one factor required for their maintenance, but involvement of other factor(s) in the conditioned medium of TBR59 stromal cells was suggested. A novel immature hematopoietic cell line, THS119, may provide an appropriate experimental system to resolve how hematopoietic cells are kept in a primitive phase within a hematopoietic microenvironment.
 ...
PMID:A novel stromal cell-dependent hematopoietic cell line established from temperature-sensitive SV40 T-antigen transgenic mice. 1037 98

Definitive hematopoiesis begins in the para-aortic, splanchnopleural (P-Sp) and aorta-gonad-mesonephros (AGM) regions of mouse embryos and then switches to the fetal liver [1] [2] [3]. Gene-targeted mice lacking the c-Myb transcription factor have severe hematopoietic defects in the fetal liver [4]. The role of c-Myb, if any, in P-Sp/AGM hematopoiesis has not been examined, however. Recently, we reported that oncostatin M can effectively expand both hematopoietic and endothelial-like cells from in vitro cultures of the AGM region [5]. Using this cell culture system, we examined the involvement of c-Myb in definitive hematopoiesis in the P-Sp and AGM regions. When primary cultures from the P-Sp or AGM regions of wild-type mouse embryos were probed with an anti-c-Myb antibody, hematopoietic cells but not endothelial-like cells showed positive staining. In contrast, in the P-Sp/AGM culture from c-myb(-/-) embryos, no hematopoietic cells were generated and endothelial-like cells predominated, indicating that the impairment of hematopoiesis in the liver of c-myb(-/-) embryos is actually preceded by a defect in P-Sp/AGM hematopoiesis. Hematogenic precursor cells were, however, still present in an inert but competent form among the endothelial-like, adherent cell population of c-myb(-/-) P-Sp/AGM cultures. When infected with a retrovirus carrying c-myb cDNA, these cultures gave rise to a significant number of hematopoietic cells. The rescued cells, unlike wild-type hematopoietic cells, were negative for c-Kit (a marker of hematopoietic progenitors), but did express other hematopoietic cell surface markers such as Mac-1, Gr-1 (myeloid markers), CD19, B220, Thy-1.2 (Iymphoid markers), and Ter119 (an erythroid marker). Thus, c-Myb plays a role in the generation of hematopoietic cells in the embryonic P-Sp and AGM regions.
 ...
PMID:Hematopoietic cells in cultures of the murine embryonic aorta-gonad-mesonephros region are induced by c-Myb. 1046 71


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>