Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Colony-stimulating factor-1 (CSF-1) is a hematopoietic growth factor that is released by osteoblasts and is recognized to play a critical role in bone remodeling in vivo and in vitro. CSF-1 is synthesized as a soluble or cell-surface protein. It is unclear, however, whether human osteoblasts express both molecular forms of CSF-1, and whether these isoforms can independently mediate osteoclastogenesis. In the present study, using a combination of quantitative reverse transcriptase polymerase chain reaction, flow cytometry, and Western immunoblot analysis, we have demonstrated that human osteoblast-like cells as well as primary human osteoblasts express the cell-surface form of CSF-1 both constitutively and in response to parathyroid hormone and tumor necrosis factor. Furthermore, using an in vitro co-culture system, we have shown that cell-surface CSF-1 alone is sufficient to support osteoclast formation. These findings may be especially significant in view of evidence that direct cell-to-cell contact is critical for osteoclast formation, and suggest that differential regulation of expression of the CSF-1 isoforms may influence osteoclast function modulated by osteotropic hormones.
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PMID:The cell-surface form of colony-stimulating factor-1 is regulated by osteotropic agents and supports formation of multinucleated osteoclast-like cells. 946 6

Thrombopoietin (TPO) is a hematopoietic growth factor which plays a central role in normal megakaryocytopoiesis and thrombopoiesis. Although the interaction between TPO and its receptor c-Mpl encoded by the c-mpl gene is now known to be implicated in the proliferation and/or differentiation of abnormal myeloid cells and normal hematopoietic stem cells, little is known about a role of the TPO/c-Mpl system in lymphoid leukemia cells. In the present study, we first examined the expression of c-mpl/c-Mpl in 23 human lymphoid leukemic cell lines (T-lineage 4, B-lineage 19) using three distinct methods. The c-mpl mRNA was detectable in as many as 20 cell lines (T-lineage 3, B-lineage 17) by reverse transcriptase-polymerase chain reaction, but its translated product, c-Mpl, was demonstrable by Western blot only in B-lineage cell lines. Flow cytometric analysis revealed the surface c-Mpl expression in 13 of 17 B-lineage cell lines, but its higher expression (>40%) was restricted in nine B-precursor cell lines, eight of which had 11q23 translocation or Philadelphia chromosome (Ph1). We also demonstrated that two of eight cell lines with 11q23 translocation or Ph1 exhibited a significant proliferative response to TPO in the 3H-thymidine uptake and colony-forming assays. Triggering of these cell lines by TPO transiently up-regulated tyrosine phosphorylation of JAK-2 and Shc, indicating that their receptor is functional. Primary leukemia cells separated from patients with B-precursor acute lymphoblastic leukemia with Ph1 or 11q23 translocation also showed the surface c-Mpl expression and a significant responsiveness to TPO. These results suggest that the TPO/c-Mpl interaction may play a physiological role in the growth regulation of B-precursor leukemia cells particularly with specific chromosomal abnormalities.
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PMID:Expression of thrombopoietin receptor and its functional role in human B-precursor leukemia cells with 11q23 translocation or Philadelphia chromosome. 1099 6

We are interested in the regulation of the tissue specificity of the megakaryocyte-specific platelet glycoprotein IIb gene. The murine embryonic stem (ES) cells are able to differentiate into erythroid, mast and granulomonocytic cells in appropriate culture conditions. Our goal is to optimize the production of myeloid cells including megakaryocytes (MKs) by ES cells. We have found that coculture with MS-5 stromal cells and the presence of a cocktail of hematopoietic growth factors (HGFs) [stem cell factor, interleukin 3 (IL-3), IL-6, IL-11, G-CSF and erythropoietin] had a high synergistic activity on differentiation of ES cells into pure and MK-containing myeloid colonies from day 12 embryoid bodies. Thrombopoietin increased the number of MKs only when added to the HGF cocktail in the presence of MS-5 cells. Interestingly, many MKs exhibited a "hairy" appearance evocative of pseudopodial proplatelet formation. Expression of genes specific for the megakaryocytic lineage, GPIIb, PF4, mpl and GPIIIa, was detected by reverse transcriptase-polymerase chain reaction (RT-PCR) during differentiation of ES cells, and their relative time course was evaluated. This demonstrates that optimized culture conditions for the differentiation of ES cells into the MK lineage provide a useful tool for the study of the regulation of expression of genes during megakaryocytopoiesis.
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PMID:Hematopoietic differentiation of embryonic stem cells: an in vitro model to study gene regulation during megakaryocytopoiesis. 1101 21

Dormant hematopoietic stem cells (HSCs) are activated by microenvironmental cues of the niche in response to the injury of bone marrow (BM). It is not clearly understood how engrafted cells respond to these cues and are involved in marrow regeneration. The purpose of this study was to decipher this cellular response in competitive environment. BM cells of CD45.2 mice were transplanted in sub-lethally irradiated CD45.1 mice. The status of the donor and recipient stem cells (LSK: Lin(-)Sca-1(+)c-Kit(+)) were determined by flowcytometry using CD45 alleles specific antibodies. The presence of long-term engraftable stem cells was confirmed by marrow repopulation assay in secondary hosts, and cell cycle status was determined by staining with Ho33342 and pyronin Y, and BrdU retention assay. The expressions of different hematopoietic growth factor genes in stromal compartment (CD45(-) cells) were assessed by real-time reverse transcriptase- polymerase chain reaction (RT-PCR). The presence of donor cells initially stimulated the proliferation of host LSK cells compared with control mice without transplantation. This was expected due to pro-mitotic and anti-apoptotic factors secreted by the donor hematopoietic cells. Upon transplantation, a majority of the donor LSK cells entered into cell cycle, and later they maintained cell cycle status similar to that in the normal mouse. Donor-derived LSK cells showed 1000-fold expansion within 15 days of transplantation. Donor-derived cells not only regenerated BM in the primary irradiated host for long-term, they were also found to be significantly involved in marrow regeneration after the second cycle of irradiation. The proliferation of LSK cells was associated with the onset of colossal expression of different hematopoietic growth factor genes in non-hematopoietic cellular compartment. Activation of donor LSK cells was found to be dynamically controlled by BM cellularity. Long-term study showed that a high level of hematopoietic reconstitution could be possible by donor cells in a sub-lethally irradiated host.
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PMID:Donor hematopoietic stem cells confer long-term marrow reconstitution by self-renewal divisions exceeding to that of host cells. 2322 99


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