PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Cell Lineage”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 253 records · Page 14Linked to original sources

Studies on T-lineage cells in human decidua of first trimester pregnancies.

T-lineage cells in human decidua of early pregnancies were tested for surface markers, proliferative response, interleukin-2 (IL-2) production, and natural killer (NK) activity. T-lineage (CD2+) cells that were obtained from decidua by the use of E-rosette formation contained fewer CD3+ mature T cells and CD4+ cells than those from the peripheral blood of the same donors, while no differences were seen in the frequencies of CD8+ cells. P55 molecules of IL-2 receptor (IL-2R/p55, Tac antigen) were hardly detected on fresh decidual T-lineage cells, though approximately 20% were positive for HLA-DR. More than a half of decidual T-lineage cells expressed CD56 molecules on their surface and killed K562 cells, the prototype target of NK cells, while most of them were negative for CD16 and CD57. Upon stimulation with IL-2, decidual T-lineage cells demonstrated dose-dependent proliferative response. In addition, they were induced to produce high amounts of IL-2 by stimulation with mitogens but not with alloantigens. These results suggest that human decidua contains high numbers of CD2+3-CD16 +/- 56+ lymphocytes and that this population responds to IL-2, produces IL-2 and mediates NK activity.

Decidua↗

Distribution of macrophage lineage cells in rat gingival tissue after topical application of lipopolysaccharide: an immunohistochemical study using monoclonal antibodies: OX6, ED1 and ED2.

To discuss the role of macrophage lineage cells on the periodontal tissue destruction, we immunohistochemically examined the phenotype and the dynamics of macrophage lineage cells 1 or 3 h or 1, 2, 3 or 7 d after topical application of LPS (5 mg/ml in physiological saline) from the rat gingival sulcus using 3 monoclonal antibodies: OX6 (antigen-presenting cells), ED1 (monocytes, macrophages and dendritic cells) and ED2 (resident macrophages). We could detect at least 3 different types of macrophage lineage cells, namely OX6+/ED1+/ED2- dendritic cells and exudate macrophages and ED2+ resident macrophages. After LPS application the majority of macrophage lineage cells accumulated in the subjunctional epithelial area were newly extravasated OX6+/ED1+/ED2- dendritic cells or macrophages. The number of these cells increased progressively with time and reached a maximum level at d 2. On the other hand, number and tissue distribution of ED2+ resident macrophages did not change. These results indicate that several types of macrophage lineage cells exist in rat gingival tissue and suggest that dendritic cells and exudate macrophages transiently accumulated after LPS application are responsible for various host immune response and tissue destruction caused by LPS.

Administration, Topical↗

Marking cell lineages in living tissues.

We have generated a novel genetic system to visualize cell lineages in living tissues at high resolution. Heat shock was used to trigger the excision of a specific transposon and activation of a fluorescent marker gene. A histone-YFP marker was used to allow identification of cell lineages and easy counting of cells. Constitutive expression of a green fluorescent membrane protein was used to provide a precise outline of all surrounding cells. Marked lineages can be induced from specific cells within the organism by targeted laser irradiation, and the fate of the marked cells can be followed non-invasively. We have used the system to map cell lineages originating from the initials of primary and lateral roots in Arabidopsis. The lineage marking technique enabled us to measure the differential contribution of primary root pericycle cell files to developing lateral root primordia. The majority of cells in an emerging lateral root primordium derive from the central file of pericycle founder cells while off-centre founder cells contribute only a minor proliferation of tissue near the base of the root. The system shows great promise for the detailed study of cell division during morphogenesis.

Arabidopsis↗

B lineage cells in the inflammatory central nervous system environment: migration, maintenance, local antibody production, and therapeutic modulation.

B cells have long played an enigmatic role in the scenario of multiple sclerosis pathogenesis. This review summarizes recent progress in our understanding of B-cell trafficking, survival, and differentiation in the central nervous system (CNS). We propose four possible routes of intrathecal immunoglobulin-producing cells. The inflammatory CNS provides a unique, B-cell-friendly environment, in which B lineage cells, notably long-lived plasma cells, can survive for many years, perhaps even for a lifetime. These new findings offer a plausible explanation for the notorious persistence and stability of cerebrospinal fluid oligoclonal bands. Furthermore, we highlight similarities and differences of intrathecal immunoglobulin production in multiple sclerosis patients and patients with other CNS inflammatory conditions. Finally, we outline the possibly double-edged effects of B cells and immunoglobulin in the CNS and discuss various therapeutic strategies for targeting the B-cell response.

Animals↗

Nasal T/natural killer (NK)-cell lymphomas are derived from Epstein-Barr virus-infected cytotoxic lymphocytes of both NK- and T-cell lineage.

The cellular nature of nasal T/natural killer (NK)-cell lymphomas (NLs) remains controversial. It is still debatable whether these represent T-cell lymphomas with extensive loss of surface antigens or are, in fact, true NK-cell lymphomas. They are associated closely with Epstein-Barr virus (EBV), to the extent that EBV-encoded small non-polyadenylated RNAs (EBER) expression can be used as a marker for the neoplastic cells. The cell lineage of this group of lymphomas was examined further by correlating immunophenotype, genotype and EBV status with the expression of cytotoxic granule-associated proteins, perforin and T-cell intracellular antigen-1 (TIA-1) in 13 cases of NL. Combined immunophenotypic and gene rearrangement analyses demonstrated that NLs can be identified clearly as either NK-cell or T-cell tumours. Nasal NK-cell lymphomas lacked clonal rearrangement of both T-cell receptor (TCR) gamma and immunogloulin heavy chain (IgH) genes and were either CD3(Leu4)-CD56+ (8 cases) or CD3(Leu4)+CD56+ (2 cases), whereas nasal T-cell lymphomas had rearranged TCRgamma and germ-line IgH genes and were either CD3(Leu4)+CD56+ (2 cases) or CD3(Leu4)+CD56- (1 case). Immunohistochemical (IH) studies showed that both perforin and TIA-1 were expressed universally in NL, irrespective of NK- or T-cell lineage. Dual labelling of TIA-1 by IH and EBER by in situ hybridisation demonstrated that the granule proteins were expressed predominantly by the EBER+ tumour cells. Our results indicate that NLs are derived from EBV-infected cytotoxic lymphocytes of both NK- and T-cell lineage. We postulate that cytotoxic lymphocytes generated during the cellular immune response to EBV infection or re-activation at the nasal region themselves may become targets for EBV infection and subsequent transformation.

Gene Rearrangement, B-Lymphocyte, Heavy Chain↗

Bone marrow-derived hemopoietic precursors commit to the T cell lineage only after arrival in the thymic microenvironment.

T lymphocytes develop in the thymus from hemopoietic precursors that commit to the T cell lineage under the influence of Notch signals. In this study, we show by single cell analyses that the most immature hemopoietic precursors in the adult mouse thymus are uncommitted and specify to the T cell lineage only after their arrival in the thymus. These precursors express high levels of surface Notch receptors and rapidly lose B cell potential upon the provision of Notch signals. Using a novel culture system with complexed, soluble Notch ligands that allows the titration of T cell lineage commitment, we find that these precursors are highly sensitive to both Delta and Jagged ligands. In contrast, their phenotypical and functional counterparts in the bone marrow are resistant to Notch signals that efficiently induce T cell lineage commitment in thymic precursors. Mechanistically, this is not due to differences in receptor expression, because early T lineage precursors, bone marrow lineage marker-negative, Sca-1-positive, c-Kit-positive and common lymphoid progenitor cells, express comparable amounts of surface Notch receptors. Our data demonstrate that the sensitivity to Notch-mediated T lineage commitment is stage-dependent and argue against the bone marrow as the site of T cell lineage commitment.

Animals↗

CXC chemokine ligand 13 and CC chemokine ligand 19 cooperatively render resistance to apoptosis in B cell lineage acute and chronic lymphocytic leukemia CD23+CD5+ B cells.

CXCL13/CXCR5 and CCL19/CCR7 play a quite important role in normal physiological conditions, but the functions of both chemokine/receptor pairs in pathophysiological events are not well-investigated. We have investigated expression and functions of CXCL13/CXCR5 and CCL19/CCR7 in CD23+CD5+ and CD23+CD5- B cells from cord blood (CB) and patients with B cell lineage acute or chronic lymphocytic leukemia (B-ALL or B-CLL). CXCR5 and CCR7 are selectively expressed on B-ALL, B-CLL, and CB CD23+CD5+ B cells at high frequency, but not on CD23+CD5- B cells. Although no significant chemotactic responsiveness was observed, CXCL13 and CCL19 cooperatively induce significant resistance to TNF-alpha-mediated apoptosis in B-ALL and B-CLL CD23+CD5+ B cells, but not in the cells from CB. B-ALL and B-CLL CD23+CD5+ B cells express elevated levels of paternally expressed gene 10 (PEG10). CXCL13 and CCL19 together significantly up-regulate PEG10 expression in the same cells. We have found that CXCL13 and CCL19 together by means of activation of CXCR5 and CCR7 up-regulate PEG10 expression and function, subsequently stabilize caspase-3 and caspase-8 in B-ALL and B-CLL CD23+CD5+ B cells, and further rescue the cells from TNF-alpha-mediated apoptosis. Therefore, we suggest that normal lymphocytes, especially naive B and T cells, use CXCL13/CXCR5 and CCL19/CCR7 for migration, homing, maturation, and cell homeostasis as well as secondary lymphoid tissues organogenesis. In addition, certain malignant cells take advantages of CXCL13/CXCR5 and CCL19/CCR7 for infiltration, resistance to apoptosis, and inappropriate proliferation.

Apoptosis↗

Ulceration induces a novel epidermal growth factor-secreting cell lineage in human gastrointestinal mucosa.

Ulceration anywhere in the gastrointestinal tract induces a novel cell lineage, which grows from the bases of existing crypts, ramifies to form a new gland, and ultimately emerges onto the mucosal surface. The lineage produces neutral mucin, shows a unique lectin-binding profile and immunophenotype, and secretes abundant immunoreactive epidermal growth factor/urogastrone (EGF/URO). All gastrointestinal stem cells can produce this cell lineage following mucosal ulceration, secreting EGF/URO to stimulate cell proliferation, regeneration and ulcer healing. This cell lineage is very commonly associated with gastrointestinal ulceration, and we propose that a major in vivo role for EGF/URO is to stimulate ulcer healing throughout the gut via induction of this cell lineage in the adjacent mucosa. EGF/URO should therefore be assessed in the conservative management of inflammatory bowel disease.

Crohn Disease↗

The mucous neck cell in the human gastric corpus: a distinctive, functional cell lineage.

There is considerable debate about whether the mucous neck cell (MNC) in the mucosa of the gastric corpus is merely a transit cell population, intermediate between gastric stem cells and the differentiated zymogenic (chief or peptic) cell lineages, or has distinct functions of its own. To cast light on these possibilities, the secretory phenotype of the MNC has been examined. Archival gastric body samples from non-ulcer dyspepsia biopsies and gastrectomies performed for peptic ulcer disease were stained with antibodies to the trefoil peptides TFF1/pS2 and TFF2/SP, pancreatic secretory trypsin inhibitor (PSTI), epidermal growth factor (EGF) and its receptor (EGFR), and to the MUC1 gene product--HMFG2. Human MNCs express PSTI, TFF1/pS2, TFF2/SP, and EGF proteins, while rat MNCs express TFF2/SP; the mucin contained in the MNCs is diastase/periodic acid Schiff (D/PAS)-positive and stains with human milk fat globulin (HMFG2). The canaliculi but not the cytoplasm of adjacent parietal cells were also decorated focally by D/PAS, by HMFG2, and by antibodies to TFF2/SP and TFF1/pS2. These findings favour the hypothesis that MNCs have a defined phenotype and are thus a separate and distinct cell lineage, secreting a number of luminally-active peptides which protect the gastric mucosa, and in particular the adjacent parietal cells, from the effects of secreted gastric acid. Moreover, a considerable degree of similarity in secretory profile is noted between MNCs and the so-called 'reparative lineages' in the gut--the ulcer-associated cell lineage (UACL) and hyperplastic polyp epithelium. If, on the other hand, the MNCs are indeed a transit population differentiating into zymogenic or peptic cells, then it is clear that having differentiated into one secretory phenotype producing a range of peptides, the MNC then proceeds to differentiate into a cell with a totally different secretory phenotype, a phenomenon unique in gastrointestinal cell lineage relationships.

Animals↗

GATA-3: an unexpected regulator of cell lineage determination in skin.

Multipotent skin stem cells give rise to epidermis and its appendages, including the hair follicle. The Lef-1/Tcf family of Wnt-regulated transcription factors plays a major role in specification of the hair shaft, but little is known about how the equally important hair channel, the inner root sheath (IRS), develops in concert to shape and guide the hair. In a microarray screen to search for transcriptional regulators of hair follicle morphogenesis, we identified GATA-3, a key regulator of T-cell lineage determination. Surprisingly, this transcription factor is essential for stem cell lineage determination in skin, where it is expressed at the onset of epidermal stratification and IRS specification in follicles. GATA-3-null/lacZ knock-in embryos can survive up to embryonic day 18.5 (E18.5), when they fail to form the IRS. Skin grafting unveiled additional defects in GATA-3-null hairs and follicles. IRS progenitors failed to differentiate, whereas cortical progenitors differentiated, but produced an aberrant hair structure. Curiously, some GATA-3-null progenitor cells expressed mixed IRS and hair shaft markers. Taken together, these findings place GATA-3 with Lef-1/Wnts at the crossroads of the IRS versus hair shaft cell fate decision in hair follicle morphogenesis. This newfound function for GATA-3 in skin development strengthens the parallels between the differentiation programs governing hair follicle and lymphocyte differentiation.

Animals↗

Identification of a metaplastic cell lineage associated with human gastric adenocarcinoma.

Metaplastic cell lineages arising in response to chronic injury are precursors for the evolution of dysplasia and adenocarcinoma. Although a subtype of intestinal metaplasia has been associated with gastric adenocarcinoma, the link between this lineage and the evolution of gastric adenocarcinoma has remained unclear. Wang et al (1998) have reported that an aberrant metaplastic cell lineage with morphological characteristics similar to Brunner's glands of the duodenum develops in the fundic mucosa of mice infected with Helicobacter felis. This metaplastic lineage expresses the trefoil peptide spasmolytic polypeptide (SP). Given the epidemiological association of Helicobacter species infection with gastric cancer, we hypothesized that this SP-expressing metaplastic (SPEM) lineage may represent a precursor to or appear commensurate with gastric adenocarcinoma. The SPEM lineage was present in 68% of fundic biopsies from patients with fundic Helicobacterpylori-associated gastritis, but was absent in biopsies of fundic mucosa from patients without H. pylori infection. In a review of archival samples from 22 resected gastric adenocarcinomas, we found the SPEM lineage in 91% of cases, typically located in mucosa adjacent to the carcinoma or areas of dysplasia. Importantly, 59% of resections showed SP immunoreactivity within dysplastic cells. These data indicate a strong association of the SPEM lineage with both chronic H. pylori infection and gastric adenocarcinoma.

Adenocarcinoma↗

Origin of the inner cell mass in mouse embryos: cell lineage analysis by microinjection.

The mouse inner cell mass is established by cells that are allocated to internal positions after the 8-cell stage. We analyzed the timing of this allocation by microinjecting two cell lineage markers, horseradish peroxidase and rhodamine-conjugated dextran, into mouse blastomeres at the 8- to 32-cell stage. Prospective analysis was performed by coinjection of peroxidase and dextran, followed by 12-22 hr of culture and staining for peroxidase activity; retrospective analysis was performed by injection of peroxidase alone and localization of sister cells without further culture. Both approaches indicated that cells are allocated to internal positions during the fourth and fifth cleavage divisions, but not the sixth cleavage division, of the mouse embryo. Thus, outer cells can have inner descendants until the late morula/early blastocyst (32-cell) stage, but cells remaining outside after the fifth cleavage division are restricted to a trophectoderm fate. This information about cell lineage indicates that the previously observed totipotency of the cleaving mammalian embryo's cells is a regulative attribute that is used in normal development.

Animals↗

Emergence of salivary gland cell lineage diversity suggests a role for androgen-independent epidermal growth factor receptor signaling.

Diversity of cell lineages within glandular organs is generated postnatally by differentiation of committed progenitor cells. Fundamental regulatory aspects of this process are not understood. The mouse submandibular salivary gland (SSG) served as model to assess the role of epidermal growth factor (EGF) receptor signaling during emergence of cell lineage diversity. Temporal fluctuations in EGF receptor mRNA levels coincident with crucial differentiative cell lineage transitions were revealed by RNase protection analyses. Between days 2 and 5, when proacinar cells are maturing and striated duct cells emerge, EGF receptor mRNA levels were highest and all differentiating cells exhibited EGF receptor immunoreactivity. EGF receptor mRNA levels then declined sharply and immunoreactivity became confined to ductal cells. At day 11 in male mice, and days 11 and 16 in females, a second increase in EGF receptor mRNA was detected coincident with emergence of granular convoluted tubule (GCT) cells. With completion of androgen-dependent GCT cell differentiation at the onset of puberty, EGF receptor mRNA levels and intensity of immunoreactivity decreased. Androgen effects on EGF receptor mRNA or immunoreactivity could not be detected. These temporally distinct patterns of EGF receptor expression suggest that this signaling pathway is a mechanism of potential importance in emergence of cell lineage diversity in a glandular organ.

Androgens↗

Automated cell lineage construction: a rapid method to analyze clonal development established with murine neural progenitor cells.

Understanding cell lineage relationships is fundamental to understanding development, and can shed light on disease etiology and progression. We present a method for automated tracking of lineages of proliferative, migrating cells from a sequence of images. The method is applicable to image sequences gathered either in vitro or in vivo. Currently, generating lineage trees from progenitor cells over time is a tedious, manual process, which limits the number of cell measurements that can be practically analyzed. In contrast, the automated method is rapid and easily applied, and produces a wealth of measurements including the precise position, shape, cell-cell contacts, motility and ancestry of each cell in every frame, and accurate timings of critical events, e.g., mitosis and cell death. Furthermore, it automatically produces graphical output that is immediately accessible. Application to clonal development of mouse neural progenitor cells growing in cell culture reveals complex changes in cell cycle rates during neuron and glial production. The method enables a level of quantitative analysis of cell behavior over time that was previously infeasible.

Algorithms↗

Understanding cell lineages as complex adaptive systems.

Stem cells may be considered complex reactive systems because of their vast number in a living system, their reactive nature, and the influence of local environmental factors (such as the state of neighboring cells, tissue matrix, stem cell physiological processes) on their behavior. In such systems, emergent global behavior arises through the multitude of local interactions among the cell agents. Approaching hematopoietic and other stem cell lineages from this perspective have critical ramifications on current thinking relating to the plasticity of these lineage systems, the modeling of stem cell systems, and the interpretation of clinical data regarding many diseases within such models.

Adaptation, Physiological↗

A novel transgenic technique that allows specific marking of the neural crest cell lineage in mice.

Neural crest cells are embryonic, multipotent stem cells that give rise to various cell/tissue types and thus serve as a good model system for the study of cell specification and mechanisms of cell differentiation. For analysis of neural crest cell lineage, an efficient method has been devised for manipulating the mouse genome through the Cre-loxP system. We generated transgenic mice harboring a Cre gene driven by a promoter of protein 0 (P0). To detect the Cre-mediated DNA recombination, we crossed P0-Cre transgenic mice with CAG-CAT-Z indicator transgenic mice. The CAG-CAT-Z Tg line carries a lacZ gene downstream of a chicken beta-actin promoter and a "stuffer" fragment flanked by two loxP sequences, so that lacZ is expressed only when the stuffer is removed by the action of Cre recombinase. In three different P0-Cre lines crossed with CAG-CAT-Z Tg, embryos carrying both transgenes showed lacZ expression in tissues derived from neural crest cells, such as spinal dorsal root ganglia, sympathetic nervous system, enteric nervous system, and ventral craniofacial mesenchyme at stages later than 9.0 dpc. These findings give some insights into neural crest cell differentiation in mammals. We believe that P0-Cre transgenic mice will facilitate many interesting experiments, including lineage analysis, purification, and genetic manipulation of the mammalian neural crest cells.

Animals↗

Disregulation of leukosialin (CD43, Ly48, sialophorin) expression in the B-cell lineage of transgenic mice increases splenic B-cell number and survival.

Leukosialin (also known as Ly48, CD43, and sialophorin) is a major cell surface sialoglycoprotein found on a variety of hematopoietically derived cells. The precise function of this molecule is poorly understood but it has been implicated in cell proliferation and intercellular adhesion. We developed a transgenic mouse model to assess leukosialin's function in vivo. Our approach was to alter mouse CD43 (mCD43) expression in the B-cell lineage where it is tightly regulated, by expressing it in peripheral B cells where it is normally absent. To drive expression of leukosialin in mature B cells, the immunoglobulin heavy chain enhancer was fused to the mCD43 gene. mCD43-immunoglobulin heavy chain enhancer transgenic mice display splenomegaly due to increased numbers of B cells. Transgenic B cells show a striking increase in their ability to survive in vitro compared to B cells from nontransgenic control mice. This prolonged survival is reflected in a decreased susceptibility to apoptosis. These observations suggest that mCD43 plays an important role in the regulation of B-cell survival. The alteration of the temporal expression, or "disregulation," of a gene in transgenic mice provides a general strategy for elucidating the in vivo role of other molecules involved in cell signaling and adhesion.

Animals↗

Distinct roles of HF-1b/Sp4 in ventricular and neural crest cells lineages affect cardiac conduction system development.

The heterogeneous cell types of the cardiac conduction system are responsible for coordinating and maintaining rhythmic contractions of the heart. While it has been shown that the cells of the conduction system are derived from myocytes, additional cell types, including neural crest cells, may play a role in the development and maturation of these specialized cell lineages. Previous work has shown that the expression of the hf-1b gene is required for specification of the cardiac conduction system. Using Cre-Lox technology, we conditionally mutated the hf-1b gene in the ventricular and the neural crest cell lineages. Cx40 immunohistochemistry on HF-1b tissue-restricted knockouts revealed a requirement for HF-1b in the cardiomyogenic lineage. Electrophysiological studies identified a second requirement for HF-1b in the neural crest-derived cells. Absence of HF-1b in the neural crest led to atrial and atrioventricular dysfunction resulting from deficiencies in the neurotrophin receptor trkC. Therefore, in this study, we document that a single transcription factor, HF-1b, acts through two separate cell types to direct distinct functions of the cardiac conduction system.

Animals↗