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At least 937 records · Page 52Linked to original sources
PubMed1997

[Stem cell-fed maturational lineages and epithelial organogenesis].

Stem cell-fed maturational lineages have long known to exist in rapidly proliferating tissues such as bone marrow, gut and epidermis. Recent studies support the hypothesis that stem cell-fed maturational lineages occur also in quiescent tissues. In this review is presented evidence for this hypothesis using liver as one of the model systems representative of quiescent tissues. In addition, studies are summarized indicating that control of growth and tissue-specific gene expression is dependent on maturational lineage mechanisms operating dynamically and sometimes synergistically in combination with gradients of regulatory signals that include hormones, growth factors and extracellular matrix components. Tissue engineering for optimal maintenance of cells and tissues ex vivo and for the development of bioartificial organs will depend on use of cells at specific maturational lineage stages, seeding them onto substrata of specific mixtures of extracellular matrix components, and culturing them in hormonally and nutritionally defined media.

Cell Differentiation↗
PubMed1997

Duodenal content reflux esophagitis in the rat: an animal model for the ulcer-associated cell lineage (UACL)?

We have studied the histological changes observed in the mucosa of 10 rats in the region of a esophagojejunostomy to evaluate it as a model for the ulcer-associated cell lineage (UACL). In man, the UACL has a distinctive morphology, proliferative organization, and pattern of trefoil peptide localization. We have therefore examined these aspects aided by immunohistochemistry and in situ hybridization to the trefoil peptides TFF1, TFF2, and TFF3. Only TFF2 was studied by immunohistochemistry, whereas the mRNAs for all three peptides were examined by in situ hybridization using 35S-labeled riboprobes. The marker MIB-1 to the Ki67 proliferation-related antigen was used to examine the proliferative organization of UACL-like changes. In all cases, columnar epithelialization of the distal esophagus was seen, and in all, glands with morphological and gene expression attributes of the UACL were identified. TFF3 mRNA localized patchily throughout the UACL, whereas TFF1 mRNA was found in the upper portions of the lineage and TFF2 mRNA and its product in the acini. These lineages showed virtually no intrinsic proliferative activity. These appearances are similar to those seen in early human UACL, and we therefore propose this that this represents the first published animal model of this lineage.

Animals↗
PubMed1998

Opposite CD4/CD8 lineage decisions of CD4+8+ mouse and rat thymocytes to equivalent triggering signals: correlation with thymic expression of a truncated CD8 alpha chain in mice but not rats.

Unselected CD4+8+ rat thymocytes, generated in vitro from their direct precursors, are readily converted to functional TCRhigh T cells by stimulation with immobilized TCR-specific mAb plus IL-2. Lineage decision invariably occurs toward CD4-8+, regardless of the timing of TCR stimulation after entry into the CD4+8+ compartment or the concentration of TCR-specific mAb used for stimulation. CD4-specific mAb synergizes with suboptimal TCR-specific mAb in inducing T cell maturation, but lineage decision remains exclusively CD4-8+. These results contrast with those obtained in mice, in which Abs to the TCR complex were shown to promote CD4+8- T cell maturation from CD4+8+ thymocytes. Surprisingly, when rat and mouse CD4+8+ thymocytes were stimulated with PMA/ionomycin under identical conditions, the opposite lineage commitment was observed, i.e., mouse thymocytes responded with the generation of CD4+8- and rat thymocytes with the generation of CD4-8+ cells. It thus seems that CD4+8+ thymocytes of the two species respond with opposite lineage decisions to strong activating signals such as given by TCR-specific mAb or PMA/ionomycin. A possible key to this difference lies in the availability of p56lck for coreceptor. supported signaling. We show that in contrast to mouse CD4+8+ thymocytes, which express both a complete and a truncated CD8 alpha-chain (CD8 alpha') unable to bind p56lck, rat thymocytes only express full-length CD8 alpha molecules. Mice, but not rats, therefore may use CD8 alpha' as a "dominant negative" coreceptor chain to attenuate the CD8 signal, thereby facilitating MHC class II recognition through the higher amount of p56lck delivered, and rats may use a different mechanism for MHC class distinction during positive selection.

Animals↗
PubMed1998

Thymic lineage commitment rather than selection causes genetic variations in size of CD4 and CD8 compartments.

During their development, immature CD4+ CD8+ thymocytes become committed to either the CD4 or CD8 lineage. Subsequent complete maturation of CD4+ and CD8+ cells requires a molecular match of the expressed coreceptor and the MHC specificity of the TCR. The final size of the mature CD4+ and CD8+ thymic compartments is therefore determined by a combination of lineage commitment and TCR-mediated selection. In humans and mice, the relative size of CD4+ and CD8+ peripheral T cell compartments shows marked genetic variability. We show here that genetic variations in thymic lineage commitment, rather than TCR-mediated selection processes, are responsible for the distinct CD4/CD8 ratios observed in common inbred mouse strains. Genetic variations in the regulation of lineage commitment open new ways to analyze this process and to identify the molecules involved.

Animals↗
PubMed1998

Developmental cell lineage.

Studies of the role of cell lineage in development began in the 1870s, fell into decline in the first half of the 20th century, and were revived in the 1960s. This revival was attended by the introduction of new and powerful analytical techniques. Cell lineage can be inferred to have a causative role in developmental cell fate in embryos in which induced changes in cell division pattern lead to changes in cell fate. Such a causative role of cell lineage is suggested also by cases where homologous cell types characteristic of symmetrical and longitudinally metameric body plan arise via homologous cell lineages. The developmental pathways of commitment to particular cell fates proceed according to a mixed typologic and topographic hierarchy, which appears to reflect an evolutionary compromise between maximizing the ease of ordering the spatial distribution of determinants of commitment and minimizing the need for migration of differentially committed embryonic cells.

Animals↗
PubMed1998

GATA-1 regulates growth and differentiation of definitive erythroid lineage cells during in vitro ES cell differentiation.

Although the importance of GATA-1 in both primitive and definitive hematopoietic lineages has been shown in vivo, the precise roles played by GATA-1 during definitive hematopoiesis have not yet been clarified. In vitro differentiation of embryonic stem (ES) cells using OP9 stroma cells can generate primitive and definitive hematopoietic cells separately, and we have introduced a method that separates hematopoietic progenitors and differentiated cells produced in this system. Closer examination showed that the expression of erythroid transcription factors in this system is regulated in a differentiation stage-specific manner. Therefore, we examined differentiation of GATA-1 promoter-disrupted (GATA-1.05) ES cells using this system. Because the GATA-1.05 mice die by 12.5 embryonic days due to the lack of primitive hematopoiesis, the in vitro analysis is an important approach to elucidate the roles of GATA-1 in definitive hematopoiesis. Consistent with the in vivo observation, differentiation of GATA-1.05 mutant ES cells along both primitive and definitive lineages was arrested in this ES cell culture system. Although the maturation-arrested primitive lineage cells did not express detectable amounts of epsilony-globin mRNA, the blastlike cells accumulated in the definitive stage showed beta-globin mRNA expression at approximately 70% of the wild type. Importantly, the TER119 antigen was expressed and porphyrin was accumulated in the definitive cells, although the levels of both were reduced to approximately 10%, indicating that maturation of definitive erythroid cells is arrested by the lack of GATA-1 with different timing from that of the primitive erythroid cells. We also found that the hematopoietic progenitor fraction of GATA-1.05 cells contains more colony-forming activity, termed CFU-OP9. These results suggest that the GATA-1.05 mutation resulted in proliferation of proerythroblasts in the definitive lineage.

Animals↗
PubMed2025

Bayesian Phylogenetic Lineage Reconstruction with Loss of Heterozygosity Mutations Derived from Single-Cell RNA Sequencing.

Mutations are acquired frequently, such t`hat each cell's genome inscribes its history of cell divisions. Loss of heterozygosity (LOH) accumulates throughout the genome, offering large encoding capacity for phylogenetic inference of cell lineage.In this chapter, we demonstrate a method, using single-cell RNA sequencing, for reconstructing cell lineages from inferred LOH events in a Bayesian manner, annotating the lineage with cell phenotypes, and marking developmental time points based on X-chromosome inactivation. This type of retrospective analysis could be incorporated into scRNA-seq pipelines and was initially developed to investigate Emx1+ cortical projection neuron and glia lineages from C57Bl/6J (B6) and CAST/EiJ (CA) interstrain F1 mice, describing progenitor cells giving rise to multiple cortical cell types through stereotyped expansion and distinct waves of neurogenesis.

Animals↗
PubMed1996

Microglial lineage species are expressed in mammalian epidermal growth factor-generated embryonic neurospheres.

The epigenetic signals and progenitor cell species involved in progressive neural maturation in the mammalian brain are poorly understood. Although these complex developmental issues can be examined in cultures of generative zone progenitor cells, analysis of signaling relationships in complex progenitor cell systems requires the meticulous definition of the cellular complement at each developmental stage. The presence of microglia within the generative zone cultures would further complicate these developmental analyses. Utilizing the microglial markers Griffonia simplicifolia B4 isolectin, carbocyanine dye-acetylated low density lipoprotein, F4/80, and Mac-1 we now report the presence of microglia within cultures of late embryonic murine epidermal growth factor-derived generative zone progenitor cells. Cytokine treatment of serially passaged epidermal growth factor-generated neurospheres altered the phenotype of the microglia in culture. Macrophage colony-stimulating factor treatment promoted the expression of spindle-shaped microglia, whereas granulocytemacrophage colony-stimulating factor treatment promoted the elaboration of flat and amoeboid microglia. Treatment with microglial-conditioned medium or 10% non-heat inactivated fetal calf serum led to an increased complement of both phenotypes. Microglia could be generated from single isolated neurospheres, and there were differences in the number of microglial lineage species obtained from distinct oligopotent progenitor cells, raising the possibility that a complement of this cellular lineage may be derived from a progenitor cell present within the generative zones. These observations indicate that microglia are present within the generative zone progenitor cell system, and this system thus represents an important experimental resource to examine the progenitor cell maturation and the origin of the microglial lineage.

Animals↗
PubMed1996

Conversion of dermal fibroblasts to a myogenic lineage is induced by a soluble factor derived from myoblasts.

The limb and axial skeletal muscles of mammals originate from somitic dermomyotome, which during early development separates to form two discrete structures, the dermatome and the myotome. The latter cell mass gives rise to the muscle-forming lineage while cells of the dermatome will form the skin dermal fibroblast population of the dorsal regions of the body. It has been generally accepted for some time that myotome-derived myoblasts were the sole source of muscle fibre nuclei, but evidence has recently been presented from several laboratories that fibroblasts can fuse with myoblasts to contribute active nuclei to the resulting myotubes. We report here an investigation into the myogenic capacity of fibroblasts. Confluent monocultures of mouse dermal fibroblasts, muscle fibroblasts, and C2C12 myoblasts each retain their individual phenotype when maintained for periods up to 7 days in culture. We also grew isolated colonies of fibroblasts and myoblasts in an arrangement which allowed free exchange of tissue culture medium between the 2 cell types. We found evidence of the conversion of dermal fibroblasts to a myogenic lineage as measured by the appearance of MyoD-positive cells expressing the muscle-specific intermediate filament desmin. In addition, dermal fibroblast cultures contained multinucleate syncytia positive for MyoD and containing sarcomeric myosin heavy chain. In contrast, muscle-derived fibroblasts showed no evidence of myogenic conversion when maintained in identical culture conditions. We prepared conditioned medium from confluent cultures of C2C12 myoblasts and added this material to confluent monocultures of either dermal or muscle fibroblasts. While muscle fibroblasts showed no phenotypic alterations, cultures of dermal fibroblasts responded to myoblast conditioned medium by converting to a myogenic lineage as judged by expression of MyoD and desmin. We conclude that a proportion of dermal fibroblasts retain a myogenic capacity into stages well beyond their early association with myoblasts in the dermomyotome.

Animals↗
PubMed1997

Lectin-binding properties of oligodendrocyte lineage cells aid in defining functionally important surface proteins.

Oligodendrocytes are the myelin-forming cells of the central nervous system. They develop from migratory and proliferative precursor cells, which differentiate to mature myelinating cells. As a first step toward investigating the expression of cell surface glycoproteins by oligodendrocyte lineage cells, we tested 14 different lectins for their binding to oligodendrocyte lineage cells. Peanut agglutinin (PNA) was the only lectin used that showed a differentiation stage-dependent binding to oligodendrocytes. PNA-binding molecules are specifically expressed by oligodendrocyte precursor cells, downregulated with differentiation, and reexpressed by mature oligodendrocytes. It was additionally observed that PNA stimulates the proliferation of oligodendrocyte precursor cells. PNA may therefore be a useful tool for isolating and characterizing important cell surface glycoproteins expressed by oligodendrocyte lineage cells.

Animals↗
PubMed2000

Oligodendrocyte lineage and the motor neuron connection.

One of the more surprising recent discoveries in glial biology has been that oligodendrocytes (OLs) originate from very restricted regions of the embryonic neural tube. This was surprising because myelinating OLs are widespread in the mature central nervous system, so there was no reason to suspect that their precursors should be restricted. What we now know about early OL development suggests that they might have as much (or more) in common with ventral neurons-specifically motor neurons (MNs)-as with other types of glia. This has implications for the way we think about glial development, function, and evolution. In this article we review the evidence for a shared MN-OL lineage and debate whether this is the only lineage that generates OLs. We decide in favour of a single embryonic lineage with regional variations along the anterior-posterior neuraxis.

Animals↗
PubMed2000

New approach to cell lineage analysis in mammals using the Cre-loxP system.

The Cre-loxP site-specific recombination system was used for cell lineage analysis in mammals. We constructed an expression plasmid, pCETZ-17, which consists of cytomegalovirus enhancer/chicken beta-actin promoter (CAG), a portion of the rabbit beta-globin gene, loxP-flanked DNA sequence (containing enhanced green fluorescent protein (EGFP) cDNA), and lacZ gene encoding E. coli beta-galactosidase (beta-gal). When circular pCETZ-17 plasmid DNA was microinjected into the pronuclei of fertilized eggs and these eggs were allowed to develop to two-cell stage, 62.8% (59/94) of the two-cell embryos exhibited distinct fluorescence in one or both blastomeres, but never expressed lacZ protein, as evaluated by histochemical staining with X-Gal, a substrate for beta-gal. When both circular plasmids, pCETZ-17 and pCAG/NCre (containing CAG and DNA sequences encoding nuclear location signal and Cre), were co-injected into fertilized eggs, almost all (87.0%, 47/54) embryos exhibited low or no fluorescence, but 51.9% (27/52) exhibited positive staining for beta-gal activity. This indicates that transient expression of the Cre recombinase gene removed the loxP-flanked DNA sequence in pCETZ-17 and then caused expression of the downstream lacZ sequence. We next microinjected pCETZ-17 into the pronuclei of fertilized eggs, cultured these injected eggs for 1 day, and collected only two-cell embryos expressing EGFP in both blastomeres. One blastomere of the EGFP-expressing two-cell embryos was microinjected with pCAG/NCre, and these treated embryos were cultured for 1 day up to four-cell stage. When the developing four-cell embryos were subjected to staining with X-Gal, cell lineage-related staining pattern for beta-gal activity was observed in most (77.8%, 7/9) embryos. These findings were further confirmed using two-cell embryos derived from a transgenic mouse line carrying CETZ-17 transgene. Thus, our system, which is based on transient expression of the Cre recombinase gene directly introduced into nuclei of embryonic cells by microinjection, is a powerful means for cell lineage analysis in mammals.

Animals↗
PubMed1999

Transcriptional regulation of lymphocyte lineage commitment.

The development of T cells and B cells from pluripotent hematopoietic precursors occurs through a stepwise narrowing of developmental potential that ends in lineage commitment. During this process, lineage-specific genes are activated asynchronously, and lineage-inappropriate genes, although initially expressed, are asynchronously turned off. These complex gene expression events are the outcome of the changes in expression of multiple transcription factors with partially overlapping roles in early lymphocyte and myeloid cell development. Key transcription factors promoting B-cell development and candidates for this role in T-cell development are discussed in terms of their possible modes of action in fate determination. We discuss how a robust, stable, cell-type-specific gene expression pattern may be established in part by the interplay between endogenous transcription factors and signals transduced by cytokine receptors, and in part by the network of effects of particular transcription factors on each other.

B-Lymphocytes↗
PubMed2001

Lineage fate alteration of thymocytes developing in an MHC environment containing MHC/peptide ligands with antagonist properties.

A18 TCR transgenic thymocytes which are H-2E(k) restricted and normally selected into the CD4 lineage, are exclusively selected into the CD8 lineage in an H-2(q) MHC background. CD8 T cell selection in the H-2(q) background is far more efficient than default selection of A18 CD8 cells on a CD4(-/-) H-2E(k +) background. This suggests the involvement of special selecting ligands. Analogues of the cognate peptide for A18 with antagonist properties for the A18 TCR have previously been shown to effect a lineage diversion from CD4 to CD8 in fetal thymic organ cultures and intriguingly the MHC(q) background contains unidentified natural MHC class II ligands which similarly show antagonist properties for the A18 TCR. Despite the presence of these unidentified MHC class II ligands in the H-2(q) background and their potential influence on developing A18 thymocytes, however, MHC class I molecules were essential for thymic selection of A18 CD8 T cells.

Animals↗
PubMed2007

Dynamic expression of the basic helix-loop-helix transcription factor neuroD in the rod and cone photoreceptor lineages in the retina of the embryonic and larval zebrafish.

NeuroD is a basic helix-loop-helix (bHLH) transcription factor critical for determining neuronal cell fate and regulating withdrawal from the cell cycle. We showed previously that, in goldfish, neuroD is expressed in the rod photoreceptor lineage, and we inferred that neuroD is also expressed in a subset of amacrine cells and nascent cone photoreceptors. Here we extended that study by examining the temporal and spatial expression pattern of neuroD in the embryonic and larval zebrafish and by identifying the cell types that express this gene. NeuroD expression in the developing zebrafish retina is dynamic, spanning early retinogenesis and the maturation of cone photoreceptors. In early retinogenesis neuroD expression expands from a small patch in the ventronasal retina, through the remaining retinal neuroepithelium. As retinogenesis progresses, neuroD expression becomes restricted to amacrine cells, immature cones, and cells of rod and cone lineages. This expression achieves an adult pattern by 96 hours postfertilization (hpf), whereupon the temporal pattern of neuroD expression in central retina is spatially recapitulated at the germinative margin. The cellular pattern of expression suggests that neuroD regulates aspects of rod and cone genesis, but through separate cellular lineages. Furthermore, neuroD is coexpressed with the cone-rod-homeobox transcription factor (Crx) in putative cone progenitors and nascent cone photoreceptors, suggesting that, in the zebrafish retina, as in other vertebrate retinas, similar genetic cascades regulate photoreceptor genesis and maturation.

Animals↗
PubMed2004

Differentiation trapping screen in live culture for genes expressed in cardiovascular lineages.

We have developed a gene trap vector that transduces an EGFP-neo fusion gene (Eno) to monitor the expression of trapped genes in living cells and embryos. Upon in vitro differentiation, most gene-trapped embryonic stem (ES) cell clones exhibited detectable green fluorescence in various specialized cell types, which can be followed in the live culture in real time. Populations of ES cell-derived cardiomyocytes, smooth muscle cells, vascular endothelial cells, and hematopoietic cells were readily recognized by their distinctive morphologies coupled with unique activities, allowing efficient screening for clones with trapped genes expressed in cardiovascular lineages. Applying G418 selection in parallel differentiation cultures further increased detection sensitivity and screening throughput by enriching reporter-expressing cells with intensified green fluorescent protein signals. Sequence analyses and chimera studies demonstrated that the expression of trapped genes in vivo closely correlated with the observed lineage specificity in vitro. This provides a strategy to identify and mutate genes expressed in lineages of interest for further functional studies.

Animals↗
PubMed2005

Second branchial arch lineages of the middle ear of wild-type and Hoxa2 mutant mice.

Our current understanding of the evolution of the mammalian middle ear was first suggested by embryological studies from the 19th century. Here, site-specific recombinase-mediated lineage tracing was used to define the second branchial arch contribution to the middle ear of wild-type and Hoxa-2 mutant embryos. The processus brevis of the malleus was found to arise from second arch tissues, making it the likely homologue of the retroarticular process of nonmammalian tetrapods. The second arch also formed a portion of the otic capsule. In light of avian lineage studies, second arch cells were probably incorporated into the otic capsule before avian and mammalian lineages diverged. In Hoxa2 mutant embryos, middle ear skeletal duplications occurred at sites where first and second arch elements are normally apposed. The dorsoventral positions at which second arch skeletal elements formed and the early migration of second arch neural crest cells were not altered by the absence of Hoxa2 function.

Alleles↗
PubMed2005

Short-term lineage analysis of dorsally derived Olig3 cells in the developing spinal cord.

We examined the migration and differentiation of cells expressing Olig3, a basic helix-loop-helix transcriptional factor, in the developing spinal cord. Distribution of Olig3 lineage cells was demonstrated with in situ hybridization and X-gal staining in an Olig3-lacZ knock-in mouse. Olig3-positive cells first appeared in the dorsal spinal cord, except for the roof plate. Some of the dorsal Olig3 lineage cells co-expressed Islet1/2, Math1, or Brn3a, markers for dorsal interneuron. LacZ-positive cells were observed in the ventral-most part of the E10.5 spinal cord, suggesting that some dorsal Olig3 lineage cells migrate into the ventral-most part by E10.5. Ventral-ward migration of dorsal cells and contribution to commissural interneurons were substantiated by electroporation of EGFP expression plasmid in the dorsal spinal cord of chick embryo. Dorsal midline cells were also LacZ-positive during development. These findings suggest that dorsal Olig3 cells contribute to dorsal midline cells and commissural interneurons at intermediate and ventral levels.

Animals↗