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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lung epithelial-specific stem cells have been localized to discrete microenvironments throughout the adult conducting airway. Properties of these cells include pollutant resistance, multipotent differentiation, and infrequent proliferation. Goals of the present study were to use Hoechst 33342 efflux, a property of stem cells in other tissues, to purify and further characterize airway stem cells. Hoechst 33342 effluxing lung cells were identified as a verapamil-sensitive side population by flow cytometry. Lung side population cells were further subdivided on the basis of hematopoietic (CD45 positive) or nonhematopoietic (CD45 negative) origin. Nonhematopoietic side population cells were enriched for stem cell antigen-1 reactivity and expressed molecular markers specific to both airway and mesenchymal lineages. Analysis of the molecular phenotype of airway-derived side population cells indicates that they are similar to neuroepithelial body-associated variant Clara cells. Taken together, these data suggest that the nonhematopoietic side population isolated from lung is enriched for previously identified airway stem cells.
Am J Physiol Lung Cell Mol Physiol 2004 Apr
PMID:Molecular phenotype of airway side population cells. 1500 31

The nonhematopoietic stromal cells of the bone marrow are critical for the development of hematopoietic stem cells into functionally competent blood cells. This study addresses the question of whether bone marrow stromal cell cultures in the Dexter system propagate multiple different mesenchymal stromal cell types or one stromal cell type that expresses multiple phenotypes. Results show that isolated single stromal cells simultaneously express transcripts associated with osteoblast, fibroblast, muscle, and adipocyte differentiation. Furthermore, isolated single stromal cells simultaneously express transcripts characteristic of epithelial cells, endothelial cells, and neural/glial cells. Isolated single stromal cells also express transcripts for CD45, CD19, CD10, CD79a, and representative proto-oncogenes and transcription factors, which are typically associated with normal and neoplastic hematopoietic cells. These findings suggest that the nonhematopoietic mesenchymal cells and the hematopoietic B-lymphocytes have a common progenitor. This is consistent with the idea that progenitor cells express genes that are characteristic of the multiple lineage paths that such cells may be capable of adopting. This study demonstrates the technical feasibility of transcriptome analysis of individual primary cell-culture grown stromal cells and supports the concept that bone marrow stromal cells are relatively homogeneous and show a phenotypic signature of potential multilineage differentiation capacity.
Blood Cells Mol Dis
PMID:Multilineage gene expression in human bone marrow stromal cells as evidenced by single-cell microarray analysis. 1297 36

Bone marrow (stem) cells can differentiate into cells in multiple tissues, including lung. Conversely, there are reports that cells of nonhematopoietic tissues (brain, muscle) can give rise to lymphohematopoietic cells. Here we show that the lung contains cells capable of giving rise to lymphohematopoietic cells when transplanted to irradiated recipients. Whole lung cell suspensions, lung side population (SP) cells, and CD45(+/-) lung cells obtained from male transgenic enhanced green fluorescent protein-expressing mice were transplanted intravenously to total body irradiated female mice. Green fluorescent cells were recovered from the circulation and phenotyped for their expression of lymphohematopoietic markers (CD3, CD4, CD8, B220, Gr-1, and Mac-1). Lung SP cells were composed of heterogeneous populations and had less ability to give rise to lymphohematopoietic cells than did bone marrow SP cells. Furthermore, the ability of cells from the lung of aged mice to generate lymphohematopoietic progeny was equivalent to that of cells from young mice. Cells from lung with radioprotective and lymphohematopoietic reconstituting abilities were CD45(+). CD45(+) cells in the lung cells have lymphohematopoietic stem/progenitor cell characteristics, and this has implications for cell or gene therapy applications.
Am J Respir Cell Mol Biol 2004 Apr
PMID:Lung cells transplanted to irradiated recipients generate lymphohematopoietic progeny. 1451 74

Alternative splicing of nascent transcripts is a widespread mechanism for altering protein expression in response to extracellular stimuli. However, little is known about the sequences that mediate signal-induced alternative splicing, complicating efforts to identify genes whose splicing may be regulated in response to a particular stimuli. Here we define a sequence element that is both the primary determinant of CD45 variable exon exclusion following T cell stimulation by PMA and is sufficient to confer activation-induced skipping of a heterologous exon. Additionally, we show that this regulatory element has homology to sequences in other signal-regulated genes, suggesting that the alternative splicing of large families of genes may be regulated by common signaling pathways.
Mol Cell 2003 Nov
PMID:A conserved signal-responsive sequence mediates activation-induced alternative splicing of CD45. 1463 88

Early theories of tumor angiogenesis suggested that preexisting vessels surrounding the tumor were the principal source of the tumor vasculature but recent evidence suggests that endothelial progenitor cells (EPC) migrate from the marrow play an important role in developing the tumor blood supply. In a mouse model, in which the vascularization of a transplantable tumor was studied after bone marrow (BM) transplantation, we show that cells that express Tie-2, Sca-1, CD31 and CD45 function as both BM EPC and primitive hematopoietic stem cells. BM cells from transgenic mice expressing green fluorescent protein (GFP) under the control of the endothelial lineage-specific Tie-2 promoter (Tie-2 /GFP) were used to reconstitute irradiated (12 Gy) wild-type mice. Five donor BM cell populations were studied: (1) whole BM; (2) Sca-1-enriched BMC; (3) GFP/Tie-2+, Sca-1+ BMC; (4) GFP/Tie-2-, Sca-1+ BMC and (5) Sca-1-depleted BMC. After 4 weeks, the mice were injected with Tg.AC tumor cells. Three weeks later, sections from the tumors were stained for CD31 and examined for Tie-2-driven GFP expression. BM-derived endothelial cells were found only in mice transplanted with bone marrow containing populations of Tie-2+, Sca-1+ cells. As few as 3500 of these cells were sufficient to radioprotect lethally irradiated mice. Thus, we conclude that a rare subset of BMC (approximately 4 x 10(-3)%) with the putative properties of hemangioblasts have an active Tie-2 promoter. Selection of Tie-2+Sca-1+ BMC enriches for marrow-derived EPCs that participate in tumor angiogenesis and cells that can provide hematopoietic reconstitution of marrow-ablated mice.
Blood Cells Mol Dis
PMID:Hematopoietic stem cells and endothelial cell precursors express Tie-2, CD31 and CD45. 1475 32

In this study, we have evaluated the proliferation and the phenotype of human plasma cells of different origins, i.e., from tonsil, peripheral blood, bone marrow as well as plasma cells generated in vitro from memory B cells. We have demonstrated that plasma cells from tonsil, peripheral blood, as well as those generated in vitro, were highly proliferating and presented a homogeneous CD45bright phenotype. In contrast, bone marrow plasma cells were heterogeneous for CD45 expression but their proliferation was restricted to the CD45bright compartment. Subsequently, their CD45 expression decreased with proliferation arrest and final maturation. We also studied the proliferation of abnormal plasma cells, i.e., peripheral blood reactive plasmacytoses and multiple myeloma (MM). All reactive plasmacytoses turned out to be homogeneous expansions of CD45bright plasma cells with unusually high labeling index. In contrast, CD45 expression was heterogeneous in MM as in normal bone marrow. However, a minor CD45bright population was also always the most proliferating one as opposed to a major population of less or non-proliferating myeloma cells characterized by a weaker or a lack of CD45 expression. In conclusion, proliferation is linked to plasma-cell generation and a CD45bright phenotype is the hallmark of the most proliferating normal, reactive as well as malignant plasma cells.
Blood Cells Mol Dis
PMID:Normal and malignant human plasma cells: proliferation, differentiation, and expansions in relation to CD45 expression. 1500 21

CD45, encoded by PTPRC in humans, is the most abundantly expressed protein on the surface of many lymphocytes. We investigated whether the extracellular region of CD45 was under positive selection in Old World primates, and whether there was differential selection across this region, particularly on exons that were involved in alternative splicing and those that were not alternatively spliced. The results show extraordinarily strong and consistent positive Darwinian selection on the extracellular part of CD45 throughout the evolution of Old World monkeys, apes and humans. Positive selection is concentrated in exons 9 and 14, which code for the previously neglected linker and fibronectin III domains. These exons have a high rate of evolution at nonsynonymous sites that is roughly twice as high as that of the intronic rate in this gene. In contrast, alternatively spliced exons 4-6, which code for the variable domains, are under weaker positive selection and are evolving more slowly than the intronic rate. These data provide a striking example of positive selection in a well-known gene that should provide an impetus for further functional studies to elucidate its species-specific function.
Mol Biol Evol 2004 Aug
PMID:Rapid evolution by positive Darwinian selection in the extracellular domain of the abundant lymphocyte protein CD45 in primates. 1501 44

This study reports on the relationship between quantitative (99m)Tc-HYNIC radiolabelled annexin V tumour uptake measurements, Fas ligand (FasL) expression, matrix metalloproteinase-9 (MMP-9) expression, microvessel density (MVD) and the number of tumour-infiltrating lymphocytes in squamous cell carcinoma of the head and neck (SCCHN) patients. Twenty-eight patients (24 men and 4 women; mean age 59 years, range 43-83 years) suffering from a primary ( n, number of patients=22) or locally recurrent ( n=6) SCCHN were studied. All patients underwent a spiral CT scan, allowing estimation of lesion size in three dimensions, and (99m)Tc-HYNIC annexin V scintigraphy within 1 week of each other. Biopsies or resection of the suspected primary tumour or local recurrence for histopathological analysis were performed on all patients within a period of 10 days following (99m)Tc-HYNIC annexin V scintigraphy. The percentage uptake of the injected dose of (99m)Tc-HYNIC annexin V in visible tumour lesions on scintigrams divided by the tumour volume, derived from CT, was related to MVD and to histological score (HSCORE) values for MMP-9 and FasL expression as well as to the number of tumour-infiltrating lymphocytes (CD45 staining). Median percentage absolute tumour uptake of the injected dose/cm(3) tumour volume derived from tomographic images was 0.0001% (SD 0.0001%) at 5-6 h p.i. (range: 0.000007-0.0003%). Mean HSCORE for MMP-9 tumour staining was 2.1 (SD 0.84). Mean HSCORE for FasL tumour staining was 2.49 (SD 0.92). At the sites of tumour containing the highest number of vessels, the mean MVD was 20 vessels/field at the hot spot (range 1-73). The median number of tumour-infiltrating lymphocytes was 500 (range 100-5,000). The percentage absolute tumour uptake of the injected dose/cm(3) tumour volume derived from tomographic images correlated linearly with FasL HSCORES( r=0.47, P=0.02). No correlation was found between the percentage absolute tumour uptake of the injected dose/cm(3) tumour volume derived from tomographic images and MMP-9 HSCORES, MVD or the number of tumour-infiltrating lymphocytes. MVD correlated significantly with MMP-9 HSCORES ( r=0.44, P=0.03).
Eur J Nucl Med Mol Imaging 2004 Jul
PMID:Relationship of 99mTc-HYNIC annexin V uptake to microvessel density, FasL and MMP-9 expression, and the number of tumour-infiltrating lymphocytes in head and neck carcinoma. 1501 4

Side population (SP) cells, a rare cell type identified by their ability to efflux the vital dye Hoechst 33342, are highly enriched for stem cell activity. Bone marrow (BM) SP cells uniformly express the pan-hematopoietic marker CD45, whereas tissue SP cells are heterogeneous in CD45 expression. In previous studies, we found that CD45 is expressed on 75% of lung SP cells. By performing whole BM transplantations, we determined that CD45-positive and CD45-negative lung SP cells are marrow derived. Transplantation of 200 highly purified BM SP cells indicated that both lung SP cell subtypes are derived from this marrow cell type. Morphologically, CD45-positive lung and BM SP cells possess similar features. They are small, round, and contain scant cytoplasm. CD45-negative lung SP cells are larger and contain abundant granular cytoplasm. Gene expression patterns for hematopoietic transcription factors GATA-1, GATA-2, and PU.1 further differentiated SP marrow and lung subtypes. By immunostaining for alpha-smooth muscle actin and cytokeratin, we found significant differences in the relative expression patterns of these markers in lung and marrow SP cell subtypes. In summary, these findings demonstrate that lung SP cells are derived from the BM and that CD45-positive and -negative subtypes can be distinguished by morphological differences and gene expression patterns.
Am J Physiol Lung Cell Mol Physiol 2004 Sep
PMID:Translational physiology: origin and phenotype of lung side population cells. 1530 96

We investigated whether stem cells (MDSC) from primary cultures of rat skeletal muscle can differentiate into the smooth muscle lineage in response to vascular endothelial growth factor (VEGF) and coculture with bladder smooth muscle cells. The MDSC were isolated from gastrocnemius muscle biopsies of normal 3-6 week-old Sprague-Dawley rats and purified by the preplate technique. Cells that took approximately 6 days to adhere to the collagen-coated flasks were termed late preplate (LP) cells, and were used in all the experiments. The early plate (EP) cells (pp1-pp4) contained some myogenic cells but were mostly fibroblasts (< 15% desmin+ cells) whereas the LP cells (pp5-pp6) were highly purified muscle-derived cells (pp6) (> 90% desmin+ cells). The muscle-derived stem cells (LP cells) were CD34+ or Sca-1+, CD45- and desmin+ by immunohistochemical staining. After two days of co-culture with bladder smooth muscle cells, about 25% of the muscle-derived stem cells were positive for alpha-smooth muscle actin (alpha-SMA)+. RT-PCR for alpha-SMA was positive in the VEGF stimulated MDSC, but negative in the absence of VEGF. In conclusion, rat muscle-derived stem cells exhibited stem cell properties (CD34+ or Sca-1+), and were not of hematogeous (CD45-) but of myogenic origin (desmin+). RT-PCR of alpha-SMA was positive in the VEGF stimulated muscle-derived stem cells.
Mol Cells 2004 Feb 29
PMID:Isolation of muscle derived stem cells from rat and its smooth muscle differentiation [corrected]. 1505 28


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