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At least 343 records · Page 19Linked to original sources
PubMed1996

Embryonic mouse lung epithelial progenitor cells co-express immunohistochemical markers of diverse mature cell lineages.

Developmental expression of marker genes representative of different mature cell types can be used to study differentiation of cell lineages. We used immunohistochemistry to study expression in developing mouse lung of calcitonin gene-related peptide (CGRP), Clara cell 10-KD protein (CC10), and surfactant protein-A (SP-A), markers that are differentially expressed in neuroendocrine cells, Clara cells, and Type II alveolar cells. Two distinct developmental phases were revealed. The earlier phase (embryonic days 13-15; E13-E15) was characterized by CGRP, CC10, and SP-A immunostaining in all epithelial cells of the distal airways, with the three patterns being virtually identical in adjacent sections. The later phase (E16-E18) was characterized by emergence of staining of the differentiated cell types. These expression patterns were recapitulated in serumless organ culture, demonstrating that information necessary to generate both phases of gene expression is present within the lung analage by E11. We conclude that CGRP, CC10, and SP-A are co-expressed in most or all cells of the distal lung epithelium at E13-E15 and later become restricted to different cell lineages. This transient expression in progenitor cells of gene products characteristic of diverse differentiated cell types may reflect an underlying mechanism of gene regulation.

Animals↗
PubMed2006

Endogenous erythropoietin system in non-hematopoietic lineage cells plays a protective role in myocardial ischemia/reperfusion.

OBJECTIVE: Recent studies suggested that erythropoietin (Epo) receptors (EpoR) are expressed not only in the hematopoietic lineage cells but also in the heart and that the administration of recombinant human Epo elicits protective effects in myocardial ischemia and reperfusion (I/R). We tested our hypothesis that endogenous Epo signals mediated by EpoR expressed in the non-hematopoietic lineage cells play a protective role against myocardial I/R injury. METHODS: Transgene-rescued EpoR null mutant mice (RES), which express EpoR exclusively in the hematopoietic lineage cells, were subjected to 30 min left coronary artery occlusion followed by reperfusion. RESULTS: Hematocrit, heart rate, blood pressure, heart weight, and echocardiographic parameters were comparable between wild-type mice (WT) and RES under the baseline condition. After 24 h of reperfusion, the infarct size in RES with I/R (RES/MI) was larger than that in WT/MI. Caspase-3 activity and number of TUNEL-positive cardiomyocytes in the ischemic area were increased in RES/MI compared with WT/MI. The extents of p38 and JNK phosphorylations in the ischemic area were significantly increased in WT/MI, but not in RES/MI as compared with corresponding sham-operated mice. Plasma Epo concentration in RES/MI did not differ from that in sham-operated RES, while that in WT/MI was peaked at 24 h post I/R. Additionally, left ventricular (LV) end-diastolic diameter was increased and LV fractional shortening tended to be reduced in the RES/MI compared with WT/MI at 21 days after I/R. CONCLUSIONS: These results suggest that the endogenous Epo-EpoR system in the non-hematopoietic lineage cells plays an important protective role against myocardial I/R injury.

Animals↗
PubMed1991

Dependence of Ca2+ and K+ current development on RNA and protein synthesis in muscle-lineage cells of the ascidian Boltenia villosa.

The early development of excitability of muscle-lineage cells of the ascidian Boltenia villosa is characterized by the appearance, just after gastrulation, of a Ca2+ current and a delayed outward K+ current, while an inwardly rectifying K+ current, present since fertilization, disappears. The muscle-lineage cells are the first cells in which we detect tissue-specific electrical properties after gastrulation. Here, we show that the development of electrical properties in these cells involves RNA and protein synthesis. If transcription or translation is blocked, the Ca2+ and outward K+ currents fail to appear, whereas the inward K+ current disappears normally. For the Ca2+ current, the sensitive period for transcription extends until just before gastrulation, while the sensitive period for translation extends until after gastrulation. The oocyte has a Ca2+ current present at about 5-10% the density of that in the muscle-lineage cells; this current disappears by gastrulation. A comparison of the oocyte and muscle Ca2+ currents indicates that they are similar in voltage dependence and inactivation mechanism. A small difference in permeability sequence can be attributed to different surface charge properties at the two stages of development.

Animals↗
PubMed1996

Specification of pituitary cell lineages by the LIM homeobox gene Lhx3.

During pituitary organogenesis, the progressive differentiation of distinct pituitary-specific cell lineages from a common primordium involves a series of developmental decisions and inductive interactions. Targeted gene disruption in mice showed that Lhx3, a LIM homeobox gene expressed in the pituitary throughout development, is essential for differentiation and proliferation of pituitary cell lineages. In mice homozygous for the Lhx3 mutation, Rathke's pouch formed but failed to grow and differentiate; such mice lacked both the anterior and intermediate lobes of the pituitary. The determination of all pituitary cell lineages, except the corticotrophs, was affected, suggesting that a distinct, Lhx3-independent ontogenetic pathway exists for the initial specification of this lineage.

Animals↗
PubMed2000

Infiltration of hematogenous lineage cells into the demyelinating central nervous system of twitcher mice.

Infiltration of hematogenous lineage cells into the central nervous system (CNS) was investigated in the twitcher mouse, a murine model of globoid cell leukodystrophy in human. The hematogenous cells were selectively labeled following intraperitoneal injection of rhodamine isothiocyanate (RhIc). The frequency of detecting Rhlc-labeled cells (Rhlc+ cells) in the twitcher CNS varied with age. RhIc+ cells were hardly detected when injection was made prior to the postnatal day (PND) 30. The number of Rhlc' cells increased thereafter peaked at PND 35-38 and declined drastically at PND 40-45. The majority of RhIc+ cells were distributed in white matter of the CNS that correlated well with the areas of demyelination and of increased microglia/macrophage population described in our earlier studies. Almost all Rhlc+ cells were double-labeled with antibody for Mac-1 and also with MHC class II. Some small cells double-labeled with RhIc and antibodies for CD4, CD8, or IL-2R were also identified. By RT-PCR, the expression of monocyte chemoattractant protein- (MCP-1) mRNA increased drastically at PND 30, peaked at PND 35, and decreased gradually after PND 40. This pattern of mRNA changes correlated well with the dynamic pattern of the infiltration of hematogenous cells into the CNS, suggesting a role of chemokine(s) in the cellular infiltration in the twitcher brain. The expression of IL-10 mRNA also increased gradually. IL-10 is a cytokine inhibitory factor and a major regulator in suppressing the inflammatory response. Thus, our results indicated that hematogenous lineage cells infiltrated in the CNS of twitcher mice, and that MCP-1 and IL-10 may play an important role in regulating the cellular recruitment.

Animals↗
PubMed1987

Cell lineage analysis in ascidian embryos by intracellular injection of a tracer enzyme. III. Up to the tissue restricted stage.

Cell lineages during embryogenesis of the ascidian Halocynthia roretzi were analyzed up until the stage where each blastomere was fated to be only a single tissue type (i.e., the tissue restricted stage) by intracellular injection of horseradish peroxidase using the iontophoretic injection method. Initially, the developmental fates of all blastomeres of the 64-cell stage embryo were examined, and thereafter, only the fates of daughter blastomeres of those blastomeres that were not tissue restricted at the 64-cell stage were traced. The developmental fates of blastomeres were highly invariant except for two candidates for "equivalence groups" (J. Kimble, J. Sulston, and J. White (1979). In "Cell Lineage, Stem Cells and Cell Determination," pp. 59-68. Elsevier, Amsterdam/New York), in which cellular interaction is suggested to be involved in the specification of the fates. The right and left a8.25 cells gave rise to the otolith and ocellus, and the right and left b8.17 cells gave rise to the spinal cord and endodermal strand in a complementary manner. No fixed relationship existed between the position of the blastomere and its derivative. Most restrictions of cell fates occurred early in cleavage. The numbers of blastomeres which generated a single type of tissue were 44 at the 64-cell stage and 94 at the 110-cell stage. Eight pairs of blastomeres had not yet become tissue restricted by the 110-cell stage. Almost complete lineages of epidermis, nervous system, muscle, mesenchyme, notochord, and endodermal tissues were described, and a fate map was constructed for the blastula. For certain tissues, the primordial cells occupied two different regions. Supplementary investigations of the lineage of muscle cells were also performed on embryos of another species, Ciona intestinalis.

Animals↗
PubMed2004

Antagonistic growth regulation of cell lines derived from human lung adenocarcinomas of Clara cell and aveolar type II cell lineage: Implications for chemoprevention.

Lung cancer continues to be the leading cause of cancer death in industrialized countries and there is an urgent need for the development of preventive treatments that inhibit the progression of initiated cells into overt lung cancer in smokers who quit. Murine pulmonary adenocarcinoma models are widely used to test prospective cancer preventive agents. These tumors are of alveolar type II cell lineage, express growth-regulating signal transduction pathways that are stimulated by epidermal growth factor and protein kinase C while being inhibited by agents that increase intracellular cyclic AMP (cAMP). By contrast, pulmonary adenocarcinomas induced in hamsters are derived from bronchial and bronchiolar Clara cells, are under beta-adrenergic receptor control and their development is promoted by agents that increase intracellular cAMP. Adenocarcinomas of either cell lineage develop in humans, raising the possibility that agents with strong chemopreventive activity in murine lung cancer models due to stimulation of cAMP may selectively promote human pulmonary adenocarcinomas derived from Clara cells. We therefore compared the effects of the beta-adrenergic agonist isoproterenol and the activator of cAMP forskolin under controlled in vitro conditions on the human pulmonary adenocarcinoma cell line NCI-H322 which expresses a Clara cell phenotype versus the human pulmonary adenocarcinoma cell line A549 which expresses features of alveolar type II cells. Our data show that isoproterenol significantly stimulated cAMP, ERK1/2 activity and DNA synthesis in NCI-H322 cells and that this response involved transactivation of the EGF receptor. By contrast, we found that isoproterenol had no effect on A549 cells whereas forskolin significantly inhibited DNA synthesis and ERK1/2 activity. Our findings are consistent with the interpretation that human pulmonary adenocarcinomas of Clara cell lineage are highly sensitive to the cancer promoting effects of beta-adrenergic agonists and other agents that stimulate cAMP whereas human cancers of the same histological family but derived from alveolar type II cells are resistant to beta-adrenergic agonists and respond with a reduction in cell growth to stimulation of cAMP. Our findings suggest that some widely advertised cancer preventive agents such as green tea, retinoids and beta-carotenes are unsafe to be used by smokers or by ex-smokers due to their tumor promoting effects via stimulation of cAMP on initiated cells of Clara cell lineage.

Adenocarcinoma↗
PubMed1987

Characteristics of heterologous anti lizard (Calotes versicolor) thymocyte serum which identify the functions of thymus-derived cell lineage.

In an attempt to study the functions of thymus derived cell lineage, two different heterologous anti-lizard thymocyte sera (ATS i.v. & ATS i.p) were raised by immunizing rabbits with viable thymocytes of Calotes versicolor. Cytotoxicity assay, nylon wool fractionation and thymectomy were employed to assess the effect of these ATS on lymphoid cells of the lizards. The results revealed that ATS i.v. contained minimum amount of irrelevant antibodies than ATS i.p; non-adherent splenocytes were enriched with ATS sensitive cells, whereas the adherent with SIg+; adult thymectomy decreased ATS sensitive cells in spleens and the density of thymic antigen (identified by the ATS) in splenic thymus derived cell lineage was much higher than on thymocytes themselves. The cells of thymic lineage identified by the ATS thus resemble those of higher vertebrates.

Animals↗
PubMed1993

Cell lineage involvement in four patients with myelodysplastic syndrome and t(1;7) or trisomy 8 studied by simultaneous immunophenotyping and fluorescence in situ hybridization.

Four patients with myelodysplastic syndrome (MDS), one with t(1;7) and three with trisomy 8, were studied by immunophenotyping and fluorescence in situ hybridization (FISH) to assess cell lineage involvement. The t(1;7) was detected using a biotin-labeled chromosome 1 centromere-specific DNA probe. This aberration was present in CD34-positive stem cells, the erythroid cell lineage (GPA+), and the granulocytic/monocytic (CD13+ and CD64+) cell lineages. We were not able to demonstrate the abnormality in the lymphoid cell lineages. In the patients with trisomy 8, the aberration was detected with chromosome 8 centromere-specific DNA probe or by chromosome in situ suppression hybridization (CISS) with a chromosome 8-specific library probe. The trisomy was detected in stem cells, erythroid precursor cells, megakaryocytes, and granulocytes/monocytes. In these MDS patients, the chromosome aberrations appear to occur only in cells of myeloid lineage.

Aged↗
PubMed1994

The kinetic organization of the ulcer-associated cell lineage (UACL): delineation of a novel putative stem-cell region.

We have examined the proliferative organization of the ulcer-associated cell lineage (UACL), in a series of human ileal tissues involved by Crohn's disease, using antibodies to trefoil peptides and Ki-67. The UACL arises in conjunction with endodermal damage and is likely to play a role in subsequent tissue repair. Our study supports the view that the UACL initially forms through extrusion from the base of a parent intestinal crypt without indigenous mitotic activity. Eventually a duct forms extending to the gut surface and within this duct a proliferative zone develops. We also confirm that the trefoil peptides pS2 and hSP, which play a major role in the repair process, are spatially segregated within the UACL with a zone of overlap in the duct. Using triple antibody labelling techniques we have demonstrated that the zone of overlap of these peptides coincides with the proliferative region and provides evidence for a novel stem cell zone.

Cell Division↗
PubMed1988

Genetic analysis of developmental mechanisms in hydra. XVIII. Mechanism for elimination of the interstitial cell lineage in the mutant strain Sf-1.

The interstitial cell lineage in mutant strain sf-1 of hydra is temperature sensitive and is lost rapidly from tissue when the animal is cultured at a restrictive temperature of 23 degrees C or higher. The mechanism responsible for this cell elimination process was investigated. Sf-1 polyps were treated at a restrictive temperature of 27 degrees C for varying lengths of time, their tissues were macerated, and the resultant dissociated cells were examined for evidence of phagocytosis after Feulgen staining. It was found that large phagocytic vacuoles were present in the cytoplasm of some epithelial cells. These vacuoles contained partially degraded cells, whose nuclei had highly-condensed and intensely Feulgen-positive chromatin granules. This indicated that, as in colchicine-treated (Campbell, 1976) or starved (Bosch and David, 1984) wild-type hydra, the epithelial cells in strain sf-1 engulfed and disintegrated other cells in the phagocytic vacuoles. The incidence of phagocytosis was higher in sf-1 tissue maintained at elevated temperature than in sf-1 tissue maintained at normal temperature. However, the observed incidence was relatively low (maximally 0.14 phagocytosed cells per epithelial cell) and appeared to be too low to account for the very rapid interstitial cell loss occurring in this strain. We concluded that elimination of the interstitial cell lineage at a restrictive temperature in strain sf-1 takes place in part by phagocytosis and in part by other yet-unidentified mechanisms (cf., Marcum et al., 1980).

Animals↗
PubMed1988

Biliary epithelial and hepatocytic cell lineage relationships in embryonic rat liver as determined by the differential expression of cytokeratins, alpha-fetoprotein, albumin, and cell surface-exposed components.

The differentiation patterns of epithelial cells in fetal rat liver were analyzed in situ and in primary culture by indirect immunofluorescence microscopy using polyvalent and monoclonal antibodies directed against cytokeratins with molecular weights of 55,000 (CK55), 52,000 (CK52), and 39,000 (CK39) and against vimentin, albumin, alpha-fetoprotein, and surface-exposed components of bile ductular cells (BDS7) and hepatocytes (HES6). The anti-CK52 antibody, which reacted with biliary ductal cells in the liver of adult rats (Germain et al., Cancer Res., 45:673, 1985; Germain et al., Cancer Res., 48: 368-378, 1988), stained essentially all of the epithelial cells of embryonic day 12 (E12) rat liver. The anti-BDS7 antibody reacted with a few cell foci, which enlarged and became more numerous at later developmental ages. At E12 essentially all of the cells were positive for albumin and alpha-fetoprotein but did not express HES6. In fact HES6 was not detected until E15 in cells with the morphology of immature hepatocytes. By E18 staining with anti-HES6 reached the level of that observed on adult rat hepatocytes. Liver cells isolated from E12 rats were seeded on fibronectin-treated dishes and their response to various combinations of growth- and differentiation-promoting factors was evaluated with respect to their capacity to express either the hepatocytic or the bile ductular phenotype. In medium supplemented with serum, insulin, dexamethasone, and dimethyl sulfoxide, the E12 cells were capable of differentiating in culture to mimic over a 6-day period the sequential phenotypic changes which occur in vivo during normal hepatoontogeny, namely the loss of CK52 and the appearance of HES6. In contrast, the addition of sodium butyrate to the above supplement mixture resulted in the massive expression of BDS7. To further assess the developmental potential of fetal rat liver cells toward the biliary epithelial cell lineage, the in vitro assay was performed using cells isolated from livers of E18 rats and also from 2-day-old (P2) and P14 rats. While a slight expression of BDS7 was induced in cell culture from E18 liver, essentially no expression was observed in cells from postnatal livers. These findings strongly suggest that the emerging hepatic tissue in rat embryo is composed of bipotential progenitor epithelial cells that are capable of differentiating along either the hepatocytic or biliary epithelial cell lineage. These observations constitute a clear demonstration of the plasticity of liver differentiation and also provide a striking example of environmental influences on liver progenitor cell differentiation.

Albumins↗
PubMed1998

Macrophage lineage cells in inflammation: characterization by colony-stimulating factor-1 (CSF-1) receptor (c-Fms), ER-MP58, and ER-MP20 (Ly-6C) expression.

Macrophage populations resident in tissues and at sites of inflammation are heterogeneous and with local proliferation sometimes evident. Using the convenient murine peritoneal cavity as an inflammation model, the appearance of macrophage lineage cells was followed with time in both thioglycollate- and sodium periodate-induced exudates. The cells were characterized by their proliferative response in vitro in response to colony-stimulating factor-1 (CSF-1) (or macrophage colony-stimulating factor [M-CSF]), particularly by their ability to form colonies in agar, in combination with flow cytometry (surface marker expression and forward and side scatter characteristics). We propose that c-Fms (CSF-1 receptor), unlike other markers, is a uniformly expressed and specific marker suitable for the detection of macrophage-lineage cells in tissues, both in the steady state and after the initiation of an inflammatory reaction. It was shown that the bone marrow myeloid precursor markers, ER-MP58 and ER-MP20 (Ly-6C), but not ER-MP12 (PECAM-1), are expressed by a high proportion of macrophage-lineage cells in the inflamed peritoneum. The macrophage colony-forming cells (M-CFCs) in a 16-hour thioglycollate-induced exudate were phenotyped as c-Fms+ERMP12-20+58+, properties consistent with their being more mature than bone marrow M-CFCs. It is proposed that ER-MP58, as well as ER-MP20, may be a useful marker for distinguishing inflammatory macrophage-lineage cells from the majority of those residing normally in tissues.

Animals↗
PubMed1996

Mast cell-lineage versus basophil lineage involvement in myeloproliferative and myelodysplastic syndromes: diagnostic role of cell-immunophenotyping.

Mast cells and blood basophils are distinct hemopoietic cells. They can be distinguished from each other and from all other lymphohemopoietic cells using antibodies against surface receptors or stored cytoplasmic molecules. In patients with myelodysplastic syndromes (MDS) or myeloproliferative syndromes (MPS), an elevation of metachromatically granulated cells (MCS) is frequently seen. These cells can be classified as basophils or mast cells using monoclonal antibodies (mAbs) against leukocyte antigens, including mast cell tryptase, c-kit (= mast cell growth factor [MGF] receptor), interleukin-3 receptor alpha chain (IL-3R alpha = CD123), and CD11b (C3biR). In a stable phase of MDS or MPS, the circulating MCS usually are basophils (histamine+, tryptase-, c-kit-, IL-3R alpha +, CD11b+). In an accelerated or terminal phase of disease, however, mast cell lineage involvement and circulating mast cell precursors (histamine+, tryptase+, c-kit+, IL-3R alpha-, CD11b-) are found in a subset of patients. The use of mAbs against mast cell antigens and granulocyte antigens is diagnostic in these patients.

Basophils↗
PubMed1986

Ultrastructural features of the cytoplasm of respective kinds of cell lineages of cleavage-arrested ascidian embryo.

We observed the ultrastructural features of the cytoplasm in the cell lineages of the cleavage-arrested embryos of the ascidian, Halocynthia roretzi, and compared them with those of the cytoplasm in the corresponding cell lineages of the normal embryos or in the corresponding tissues of the normal larva, in order to examine the presence or the degree of the cellular differentiation without the cleavage. The cleavage of the embryos was arrested by the cytochalasin B at the 16-cell and the embryos were cultured in sea water containing cytochalasin B until the developmental time equivalent to the hatching of the control larva. As a result, the cytoplasmic components in the cleavage-arrested 16-cell embryos resembled those observed in the corresponding tissues of the normal larvae, especially in the b5.3 and b5.4 blastomers (epidermal lineage cells) and in the B5.1 blastomeres (which give rise to the endodermal, mesenchymal and muscle cells) but they were less uniformly organized and their polarity or orientation was very random and irregular, compared with those in the normal larvae. These results demonstrated that the morphological differentiation similar to the larval tissue differentiation could proceed even in the cleavage-arrested embryos to a certain extent.

Acetylcholinesterase↗
PubMed2000

Human bone marrow stromal cell: coexpression of markers specific for multiple mesenchymal cell lineages.

The role of hematopoietic stem cells in blood cell development is reasonably understood, whereas the identity and the function of bone marrow stromal cells are much less clear. Using stromal cells in bone marrow cultures of the Dexter type, a favorite medium for the study of hematopoiesis, we show that stromal cells actually represent a unique cell type. Conventional wisdom has held that stromal cells in Dexter cultures comprise a mixture of macrophages, hematopoietic cells, adipocytes, osteoblasts, fibroblasts, muscle cells, and endothelial cells. Our findings demonstrate that Dexter cultures consist of three cell types: macrophages ( approximately 35%), hematopoietic cells ( approximately 5%), and nonhematopoietic cells ( approximately 60%). We have purified the nonhematopoietic cells free of macrophages and hematopoietic cells to produce compelling evidence that they in fact represent a single cell type (multidifferentiated mesenchymal progenitor cell, MPC) which coexpresses genes specific for various mesenchymal cell lineages including adipocytes, osteoblasts, fibroblasts, and muscle cells. We further show that these multi- or pluridifferentiated MPCs are capable of supporting hematopoiesis by demonstrating the expression of several hematopoietic growth factors and extracellular matrix receptors including G-CSF, SCF, VCAM-1, ICAM-1, and ALCAM. Since the MPCs can be easily purified to near homogeneity (95%), they can be of value in enhancing engraftment of hematopoietic stem cells. Also, this new understanding of bone marrow stromal cells as "one cell with many different faces" promises to advance our knowledge of regulatory cellular interactions within bone marrow.

Bone Marrow Cells↗