Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Lineage”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

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

At least 973 records · Page 54Linked to original sources

Differential expression of caudal and dorsal genes in the teloblast lineages of the oligochaete annelid Tubifex tubifex.

We have cloned homologues (designated Ttu-cdx and Ttu-dl) of caudal and dorsal genes from the oligochaete annelid Tubifex tubifex. In situ hybridization revealed that Ttu-cdx begins to be expressed around the time of completion of ectodermal teloblastogenesis (i.e., the onset of gastrulation). At this time, Ttu-cdx expression is detected in a few cells that are located in the anteriormost part of the mesodermal germ bands (GBs). As development proceeds and the GBs elongate, the domain of Ttu-cdx-expressing cells in the GBs extends posteriorly. During this process, M teloblasts and primary blast cells remained negative for Ttu-cdx expression. This Ttu-cdx expression pattern is in sharp contrast to the posterior caudal expression in other organisms. Expression of Ttu-dl is detected from the one-cell stage through to the gastrula stage. Although Ttu-dl is expressed in most blastomeres, there are regional differences in Ttu-dl expression levels. During early cleavage, a large amount of Ttu-dl mRNA, which is supplied maternally, is inherited by D-cell line micromeres 2d and 4d; the remaining micromeres and macromeres inherit relatively small amounts of Ttu-dl transcripts. Another regional difference in Ttu-dl expression levels is seen in the ectodermal GB that is comprised of four bast-cell bandlets. The ventralmost bandlet (N lineage) exhibits the highest level of Ttu-dl expression with the lowest level in the two middle bandlets (O and P lineages) and an intermediate level in the dorsalmost bandlet (Q lineage).

Amino Acid Sequence↗

A membrane-located glycosphingolipid of monocyte/granulocyte lineage cells induces growth arrest and triggers the lytic viral cycle in Epstein-Barr virus genome-positive Burkitt lymphoma lines.

Gangliosides are known to influence cell growth and differentiation. The neolacto series ganglioside IV3NeuAc-nLc4 (2-->3-sialosylparagloboside) is present in members of the monocyte/granulocyte lineage, but is not found in cells that belong to the lymphocyte lineage. In this study we demonstrated that IV3NeuAc-nLc4 inhibits the proliferation of Epstein-Barr virus (EBV) genome-positive Burkitt lymphoma cells of the lines Raji and P3HR-1K. IV3NeuAc-nLc4-induced growth inhibition is associated with an increase in G0/G1 phase cells and a reduced expression of CD21 and HLA-DR antigens on Raji cells. These data suggest that IV3NeuAc-nLc4 may affect differentiation of lymphoma cells. Additionally, the increased expression of viral mRNA species which are characteristic for the lytic viral cycle in the non-producer line Raji and the enhanced release of virions from the producer line P3HR-1K demonstrate that IV3NeuAc-nLc4 activates the replication of EBV. Growth inhibition and termination of the viral latency suggest that IV3NeuAc-nLc4 present in monocyte/granulocyte lineage cells may be an effector of the natural defense against EBV persistency and transformation.

Apoptosis↗

GABAergic lineage differentiation of AF5 neural progenitor cells in vitro.

We have previously described an immortal rat central-nervous-system progenitor cell line, AF5, which is able to exit the cell cycle and assume a differentiated state with neuronal properties. The phenotypic specification of differentiated AF5 cells, however, is not known. In the present study, when induced to differentiate by serum starvation in Neurobasal medium, AF5 cells down-regulate glial fibrillary acidic protein and up-regulate expression of beta-III-tubulin, medium-molecular-weight neurofilament protein, and neuronal growth-associated protein 43. Expression of the gamma-aminobutyric acid (GABA) lineage marker, glutamic acid decarboxylase 67 (GAD67), increases during differentiation, suggesting that AF5 cells adopt a GABAergic lineage. Time-course analysis of the GABAergic neuron specification transcription factor, Pitx2, by reverse transcription/polymerase chain reaction, has shown an increase in the Pitx2 transcript 48 h after initiation of differentiation. In differentiated AF5 cells, expression of the Pitx2 target gene products GAD65 and GABA transporter-1 increases. Cellular GABA levels in differentiated AF5 cells increase by about 26-fold, and GABA release into the medium is 150-fold higher compared with that of undifferentiated cells. Therefore, AF5 cells can be induced to differentiate to a neuronal phenotype with a GABAergic lineage.

Animals↗

Osteoblast lineage properties in giant cell tumors of bone.

BACKGROUND: Giant cell tumors of bone (GCTs), among the most common primary bone tumors, are characterized by the formation of abundant osteoclast-like multinucleated giant cells (MNCs). It is not yet clear about the origin of GCTs and which cells in the lesion are the true neoplastic component. Several recent reports suggested that MNCs are osteoclasts induced by stroma-like tumor cells expressing the ligand for receptor activator of NF-kappaB (RANKL), which is a membrane-bound osteoclast differentiation factor. This hypothesis suggests an osteoblast lineage origin of GCTs, although it has long been speculated about GCTs being of mesenchymal stem cell (MSC) origin. METHODS: We investigated the expression of osteoblastic differentiation markers in 10 human GCTs by reverse transcription-polymerase chain reaction and immunohistochemistry. We also performed osteoblastic and adipogenic differentiation assays using cultured cells derived from surgically resected lesions to estimate the stem cell-like properties. RESULTS: GCTs and derived stromal cells expressed many osteoblast lineage marker genes, such as collagen type I, bone sialoprotein, core binding factor a-1, and osteocalcin. Instead of stable expression of mRNA, osteocalcin was not detected among the proteins. The tumor-derived cultures showed osteoblastic but not adipogenic differentiation capability. These findings strongly suggest that GCTs are of osteoblast lineage origin. CONCLUSIONS: Our results indicated that GCTs expressed many osteoblastic markers and showed properties of pre-osteoblast-like cells rather than those of MSCs. These observations may provide some insight into the mechanisms of disease progression and the origin of GCTs.

Adolescent↗

Genetic origins of the Ainu inferred from combined DNA analyses of maternal and paternal lineages.

The Ainu, a minority ethnic group from the northernmost island of Japan, was investigated for DNA polymorphisms both from maternal (mitochondrial DNA) and paternal (Y chromosome) lineages extensively. Other Asian populations inhabiting North, East, and Southeast Asia were also examined for detailed phylogeographic analyses at the mtDNA sequence type as well as Y-haplogroup levels. The maternal and paternal gene pools of the Ainu contained 25 mtDNA sequence types and three Y-haplogroups, respectively. Eleven of the 25 mtDNA sequence types were unique to the Ainu and accounted for over 50% of the population, whereas 14 were widely distributed among other Asian populations. Of the 14 shared types, the most frequently shared type was found in common among the Ainu, Nivkhi in northern Sakhalin, and Koryaks in the Kamchatka Peninsula. Moreover, analysis of genetic distances calculated from the mtDNA data revealed that the Ainu seemed to be related to both the Nivkhi and other Japanese populations (such as mainland Japanese and Okinawans) at the population level. On the paternal side, the vast majority (87.5%) of the Ainu exhibited the Asian-specific YAP+ lineages (Y-haplogroups D-M55* and D-M125), which were distributed only in the Japanese Archipelago in this analysis. On the other hand, the Ainu exhibited no other Y-haplogroups (C-M8, O-M175*, and O-M122*) common in mainland Japanese and Okinawans. It is noteworthy that the rest of the Ainu gene pool was occupied by the paternal lineage (Y-haplogroup C-M217*) from North Asia including Sakhalin. Thus, the present findings suggest that the Ainu retain a certain degree of their own genetic uniqueness, while having higher genetic affinities with other regional populations in Japan and the Nivkhi among Asian populations.

Asian People↗

Reframing early gastric carcinogenesis through lineage, niche, and evolution.

Early gastric cancer is still commonly conceptualized as the endpoint of a linear sequence from chronic gastritis to intestinal metaplasia, dysplasia, and invasion. Yet recent single-cell, spatial, genomic, and functional studies indicate that this model incompletely captures the biology of early gastric carcinogenesis. Malignant potential is established progressively within a precancerous gastric field already shaped by somatic evolution, chronic inflammatory injury, and epithelial lineage distortion. Within this field, progression is concentrated in a restricted set of precursor states, particularly incomplete, hybrid, and stem-like metaplastic populations that display plasticity, persistence, and increasing compatibility with a supportive microenvironment. Fibroblast niche remodeling, immune protection loss, endothelial rewiring, genomic instability, epigenetic drift, and selective retention of advantageous molecular alterations further promote malignant commitment. In parallel, diffuse gastric cancer appears to follow a distinct route that may arise independently of conventional intestinal metaplasia through E-cadherin-deficient epithelial transformation and downstream chromatin reprogramming. Here, we synthesize recent evidence to propose an updated framework for early gastric carcinogenesis based on field evolution, lineage instability, ecosystem support, and pathway divergence. Rather than replacing the classical Correa cascade, this framework seeks to refine it by shifting the unit of risk assessment from histologic stage alone to biologically defined precursor states shaped by lineage instability, clonal persistence, niche permissiveness, and pathway-specific molecular constraints. This perspective shifts the emphasis of prevention from detecting smaller cancers to identifying and intercepting biologically committed precursor states before invasion occurs.

Humans↗

Leukemia inhibitory factor induces multi-lineage differentiation of adult stem-like cells in kidney via kidney-specific cadherin 16.

Side population (SP) is reported to be a stem cell-rich population. In the presence of leukemia inhibitory factor (LIF), cultured kidney SP cells differentiated into multi-lineage in collagen gel but not in synthesized polymer that has no cell adhesion factor. In cultured kidney SP cells, gene expression of kidney-specific cadherin 16 was specifically upregulated in collagen gel but not in synthesized polymer. Moreover, decreasing cadherin 16 expression using siRNA abolished LIF-induced multi-lineage differentiation of kidney SP in collagen gel. These results indicated that LIF induced multi-lineage differentiation of adult stem-like cells in kidney via cadherin 16.

Animals↗

Homeodomain-mediated beta-catenin-dependent switching events dictate cell-lineage determination.

While the biological roles of canonical Wnt/beta-catenin signaling in development and disease are well documented, understanding the molecular logic underlying the functionally distinct nuclear transcriptional programs mediating the diverse functions of beta-catenin remains a major challenge. Here, we report an unexpected strategy for beta-catenin-dependent regulation of cell-lineage determination based on interactions between beta-catenin and a specific homeodomain factor, Prop1, rather than Lef/Tcfs. beta-catenin acts as a binary switch to simultaneously activate expression of the critical lineage-determining transcription factor, Pit1, and to repress the gene encoding the lineage-inhibiting transcription factor, Hesx1, acting via TLE/Reptin/HDAC1 corepressor complexes. The strategy of functionally distinct actions of a homeodomain factor in response to Wnt signaling is suggested to be prototypic of a widely used mechanism for generating diverse cell types from pluripotent precursor cells in response to common signaling pathways during organogenesis.

Animals↗

Myeloid lineage cell-restricted insulin resistance protects apolipoproteinE-deficient mice against atherosclerosis.

Inflammatory processes play an important role in the pathogenesis of vascular diseases, and insulin-resistant diabetes mellitus type 2 represents an important risk factor for the development of atherosclerosis. To directly address the role of insulin resistance in myeloid lineage cells in the development of atherosclerosis, we have created mice with myeloid lineage-specific inactivation of the insulin receptor gene. On an ApoE-deficient background, MphIRKO mice developed smaller atherosclerotic lesions. There was a dramatic decrease in LPS-stimulated IL-6 and IL-1beta expression in the presence of macrophage autonomous insulin resistance. Consistently, while insulin-resistant IRS-2-deficient mice on an ApoE-deficient background display aggravated atherosclerosis, fetal liver cell transplantation of IRS-2(-/-) ApoE(-/-) cells ameliorated atherosclerosis in Apo-E-deficient mice. Thus, systemic versus myeloid cell-restricted insulin resistance has opposing effects on the development of atherosclerosis, providing direct evidence that myeloid lineage autonomous insulin signaling provides proinflammatory signals predisposing to the development of atherosclerosis.

Adoptive Transfer↗

Blood cells of Drosophila: cell lineages and role in host defence.

Drosophila haemopoiesis gives rise to three independent cell lineages: plasmatocytes, crystal cells and lamellocytes. The regulation of Drosophila stem cell proliferation and lineage specification involves transactivators and signalling pathways, many of which have mammalian counterparts that control haemopoietic processes. Drosophila plasmatocytes are professional phagocytes that resemble the monocyte/macrophage lineage, crystal cells play a critical role in defence-related melanisation, and lamellocytes encapsulate large invaders. Crystal cells and lamellocytes have no clear mammalian homologues. Research into the molecular mechanisms that underlie the various immune functions of Drosophila blood cells, such as non-self recognition, is now taking wing.

Animals↗

T lineage progenitors: the earliest steps en route to T lymphocytes.

T lymphocyte development in the thymus is a tightly regulated stepwise process. The identification and characterization of the earliest T lineage progenitors and their downstream progeny now enables the study of important cellular and molecular mechanisms that control and regulate T lineage commitment and differentiation. Significant progress has been made recently on the developmental relationships of the various cells with T cell progenitor activity identified in mouse bone marrow, blood and thymus, and on the molecular regulation of progenitor homing to the thymus. The essential role of Notch-1 signalling in intrathymic T lineage commitment and subsequent T cell development has been clearly documented.

Animals↗

Tn125-borne blaNDM-1 is decoupled from clonal background in a transcontinental Acinetobacter baumannii ST126/KL14 lineage.

BACKGROUND/OBJECTIVES: Carbapenem-resistant A. baumannii (CRAB) is a WHO Critical Priority pathogen. The blaNDM-1-carrying ST126/KL14 lineage has been independently reported from Vietnam (2015), Malaysia (2016), the USA (2023-2026), and Costa Rica (2024). Whether these geographically distinct reports represent a single transcontinental clone and through what mechanism blaNDM-1 disseminates has not been formally tested. METHODS: We performed comprehensive whole-genome reanalysis of the Vietnamese sentinel isolate DMS06669_L1 using three nested panels (n = 19, n = 138, and n = 609 Vietnamese A. baumannii genomes) and surveyed 429 plasmids extracted from 99 NDM-1 A. baumannii genomes retrieved from NCBI Pathogen Detection. RESULTS: Four ST126/KL14 isolates share high inter-regional average nucleotide identity (ANI; 99.77-99.92%) but wide intra-clade core-SNP distances (41-731 SNPs, well above the ∼20-40-SNP range typical of single-outbreak transmission clusters) and lack a significant molecular clock, consistent with a related transcontinental lineage rather than a single recent clone. NDM-1 plasmid evolution is statistically uncorrelated with chromosomal sequence type (Spearman ρ = 0.131, P = 0.573). At 609-strain population scale, under a fragmentation-aware detection criterion, all 41 blaNDM-1-carrying Vietnamese strains also carry ISAba125, with none carrying blaNDM-1 without it (Fisher exact test; Haldane-Anscombe-corrected OR ≈2.0 × 10³, 95% CI 1.2 × 10² to 3.4 × 10⁴; P = 4.74×10⁻⁴⁸; φ = 0.79). CONCLUSIONS: The blaNDM-1 dissemination pattern in this ST126/KL14 lineage is primarily consistent with Tn125 transposition acting alongside plasmid-borne spread. Standard MLST-based surveillance is insufficient; multi-level genomic monitoring - including chromosomal and plasmid-level detection of the Tn125/ISAba125 unit - is required to track this resistance threat.

A. baumannii↗

Perspective: stem cells react! Cell lineages as complex adaptive systems.

It may be argued that adult stem cell processes or, more precisely, the cell lineages that arise from them, represent complex reactive or adaptive systems. Approaching hematopoietic and other stem cell lineages from this perspective has direct bearing on current debates regarding the plasticity of these lineage systems as well as on interpretation and modeling of clinical data regarding many diseases.

Adaptation, Physiological↗

Normal specification of the extraembryonic lineage after somatic nuclear transfer.

To examine the establishment and maintenance of trophectoderm (TE) lineage in somatic cloned blastocysts, the expression of Cdx2, a key molecule for specification of TE fate, was immunohistochemically examined simultaneously with Oct4 expression. Cloned mouse embryos were made by nuclear transfer using cumulus cells, tail-tip fibroblasts, and embryonic stem cells. After 96 h of culture, the rates of Oct4-expressing blastocysts were as low as 50% and 60% for cumulus and fibroblast clones, respectively. However, regardless of Oct4 expression, the majority of those cloned blastocysts (> 90%) normally expressed Cdx2. Thus, even though somatic cloned embryos have reduced potential to produce the inner cell mass lineage, the TE lineage can be established and maintained.

Animals↗

Transient suppression of PPARgamma directed ES cells into an osteoblastic lineage.

Osteoblasts and adipocytes are believed to share a common progenitor. Peroxisome proliferator-activated receptor gamma (PPARgamma) plays a key role in the switching of these two cell lineages. Here, we demonstrated the differentiation of ES cells into an osteoblastic lineage using siRNA against PPARgamma without the addition of any osteogenic factors. We found that PPARgamma-siRNA downregulated the expression of aP2 mRNA and lipid accumulation, whereas it upregulated the expression of osteocalcin and calcium deposition. These results suggested that ES cells were directed into an osteoblastic lineage. Therefore, transient suppression using PPARgamma-siRNA may be a novel tool to induce differentiation of ES cells into osteoblasts.

Adipocytes↗

Decoding bipotency: a transient regulatory state bridging totipotency and lineage commitment.

Early mammalian embryogenesis entails a coordinated transition from totipotency to the first lineage bifurcation, giving rise to embryonic lineages and the extra-embryonic trophectoderm. The mechanisms by which totipotency is resolved into lineage-primed states remain incompletely understood. Emerging evidence supports a non-binary model in which cells traverse a continuum of potency states, passing through a transient bipotent intermediate that retains both embryonic and extra-embryonic potential while exiting totipotency. Here, we synthesize recent advances in the mechanisms that establish, maintain, and resolve bipotency. We emphasize the coordinated roles of transposable elements, transcription factors, and signaling pathways in regulating this transition. We also highlight newly developed bipotent stem cell models and their implications in generating advanced embryo models in vitro. Notably, current insights are largely derived from mouse systems; given key differences between mouse and human early embryogenesis, extending these findings to human models remains a critical next step.

Animals↗

Modulation of coreceptor transcription during positive selection dictates lineage fate independently of TCR/coreceptor specificity.

For developing T cells, coreceptor choice is matched to T cell antigen receptor (TCR) MHC specificity during positive selection in the thymus, but the mechanism remains uncertain. Here, we document that TCR-mediated positive selection signals inactivate the immature CD8(III) enhancer in double positive (DP) thymocytes, explaining in part the cessation of CD8 coreceptor transcription that occurs during positive selection. More importantly, by placing CD4 protein expression under the control of CD8 transcriptional regulatory elements, we demonstrate that cessation of CD4 coreceptor transcription during positive selection results in precisely the same lineage fate as cessation of CD8 coreceptor transcription. That is, MHC-II-signaled DP thymocytes differentiated into CD8-lineage cytotoxic T cells, despite the MHC-II specificity and CD4 dependence of their TCRs. This study demonstrates that termination of coreceptor transcription during positive selection promotes CD8-lineage fate, regardless of TCR specificity or coreceptor protein identity.

Animals↗

Stage-specific and differential notch dependency at the alphabeta and gammadelta T lineage bifurcation.

Signals transduced by Notch receptors are indispensable for T cell specification and differentiation of alphabeta T lineage cells. However, the role of Notch signals during alphabeta versus gammadelta T lineage decision remains controversial. Here, we addressed this question by employing a clonal analysis of CD4(-)CD8(-) (DN) progenitor potential to position the divergence of alphabeta and gammadelta T cell lineages to the late DN2 to DN3 developmental stages. Accordingly, alphabeta and gammadelta precursor frequencies within these T cell progenitor subsets were determined, both in the presence and absence of Notch signaling through Delta-like 1. Notch signals were found to be critical for the DN to CD4(+)CD8(+) (DP) transition, irrespective of the identity (pTalphabeta or gammadelta) of the inducing T cell receptor complex, whereas gammadelta T cells developed from gammadeltaTCR-expressing T cell progenitors in the absence of further Notch ligand interaction. Collectively, our findings demonstrate a differential, stage-specific requirement for Notch receptor-ligand interactions in the differentiation of alphabeta and gammadelta T cells from T cell progenitors.

Animals↗