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At least 73 records · Page 4Linked to original sources
PubMed1999

Cell lineage of the midline cells in the amphipod crustacean Orchestia cavimana (Crustacea, Malacostraca) during formation and separation of the germ band.

Cell lineages of identified midline cells were traced in the amphipod Orchestia cavimana (Crustacea, Malacostraca) by in vivo labelling. Midline cells are a common phenomenon in the germ band of crustaceans and insects. Studies in midline cells of Drosophila showed an origin from separate, paired anlagen and a differentiation into three types of cells. The in vivo labelling of midline cells of Orchestia demonstrates that they originate from the same material as the neural and epidermal ectoderm, divide in a stereotyped cell division pattern and give rise to at least two different types of cells. During the following evolutionarily derived mode of germ band elongation in Orchestia, a morphogenetic process is intercalated that separates germ band halves. On the level of single cells, it can be shown that midline cells are the only ectodermal cells that bridge the large distance between the separated parts. The cells are stretched extensively but do not proliferate. Comparing the midline cells of Orchestia with non-malacostracan crustaceans and insects, the results favour the hypothesis that midline cells are a distinct population of cells homologous in crustaceans and insects.

Animals↗
PubMed2006

A CTX family cell adhesion molecule, JAM4, is expressed in stem cell and progenitor cell populations of both male germ cell and hematopoietic cell lineages.

Stem cells are maintained in an undifferentiated state by interacting with a microenvironment known as the "niche," which is comprised of various secreted and membrane proteins. Our goal was to identify niche molecules participating in stem cell-stem cell and/or stem cell-supporting cell interactions. Here, we isolated genes encoding secreted and membrane proteins from purified male germ stem cells using a signal sequence trap approach. Among the genes identified, we focused on the junctional adhesion molecule 4 (JAM4), an immunoglobulin type cell adhesion molecule. JAM4 protein was actually localized to the plasma membrane in male germ cells. JAM4 expression was downregulated as cells differentiated in both germ cell and hematopoietic cell lineages. To analyze function in vivo, we generated JAM4-deficient mice. Histological analysis of testes from homozygous nulls did not show obvious abnormalities, nor did liver and kidney tissues, both of which strongly express JAM4. The numbers of hematopoietic stem cells in bone marrow were indistinguishable between wild-type and mutant mice, as was male germ cell development. These results suggest that JAM4 is expressed in stem cells and progenitor cells but that other cell adhesion molecules may substitute for JAM4 function in JAM4-deficient mice both in male germ cell and hematopoietic lineages.

Animals↗
PubMed1996

Lineage-specific regulators couple cell lineage asymmetry to the transcription of the Caenorhabditis elegans POU gene unc-86 during neurogenesis.

The POU homeo box gene unc-86 specifies neuroblast and neural identities in the developing Caenorhabditis elegans nervous system. After an asymmetric neuroblast division, unc-86 is expressed in one of two daughter cells in 27 lineage classes that are not obviously related by function or position. We show here that unc-86 transcriptional regulatory regions detect cell lineage asymmetry to activate unc-86 expression in one of two neuroblast daughter cells. Distinct regulatory regions activate unc-86 expression in particular sets of sublineages. Therefore the unc-86 regulatory region integrates distinct cell lineage asymmetry cues to activate unc-86 expression in the many classes of neuroblast cell lineages. In agreement with such lineage-specific regulation of unc-86 asymmetric activation, mutations in lin-11 (LIM homeo box), ham-1, and lin-17 affect the asymmetry of unc-86 expression in particular cell lineages, and mutations in lin-32 (achaete/scute family), vab-3 (Pax-6 homolog) and egl-5 (Abd-B homolog) affect the establishment of unc-86 expression in other cell lineages. Homologs of unc-86 and many of these unc-86 regulators have been implicated in control of neurogenesis in vertebrates and invertebrates. These data suggest that unc-86 acts in a phylogenetically conserved pathway that couples neuroblast cell lineage asymmetry to the generation of diverse neural types.

Animals↗
PubMed2005

Applications of mRNA injections for analyzing cell lineage and asymmetric cell divisions during segmentation in the leech Helobdella robusta.

Synthetic mRNAs can be injected to achieve transient gene expression even for 'non-model' organisms in which genetic approaches are not feasible. Here, we have used this technique to express proteins that can serve as lineage tracers or reporters of cellular events in embryos of the glossiphoniid leech Helobdella robusta (phylum Annelida). As representatives of the proposed super-phylum Lophotrochozoa, glossiphoniid leeches are of interest for developmental and evolutionary comparisons. Their embryos are suitable for microinjection, but no genetic approaches are currently available. We have injected segmentation stem cells (teloblasts) with mRNAs encoding nuclear localized green fluorescent protein (nGFP) and its spectral variants, and have used tandem injections of nGFP mRNA followed by antisense morpholino oligomer (AS MO), to label single blast cell clones. These techniques permit high resolution cell lineage tracing in living embryos. We have applied them to the primary neurogenic (N) lineage, in which alternate segmental founder cells (nf and ns blast cells) contribute distinct sets of progeny to the segmental ganglia. The nf and ns blast cell clones exhibit strikingly different cell division patterns: the increase in cell number within the nf clone is roughly linear, while that in the ns clone is almost exponential. To analyze spindle dynamics in the asymmetric divisions of individual blast cells, we have injected teloblasts with mRNA encoding a tau::GFP fusion protein. Our results show that the asymmetric divisions of n blast cells result from a posterior shift of both the spindle within the cell and the midbody within the mitotic spindle, with differential regulation of these processes between nf and ns.

Animals↗
PubMed2007

Activation of the Hedgehog signaling pathway in T-lineage cells inhibits TCR repertoire selection in the thymus and peripheral T-cell activation.

TCR signal strength is involved in many cell fate decisions in the T-cell lineage. Here, we show that transcriptional events induced by Hedgehog (Hh) signaling reduced TCR signal strength in mice. Activation of Hh signaling in thymocytes in vivo by expression of a transgenic transcriptional-activator form of Gli2 (Gli2DeltaN(2)) changed the outcome of TCR ligation at many stages of thymocyte development, allowing self-reactive cells to escape clonal deletion; reducing transgenic TCR-mediated positive selection; reducing the ratio of CD4/CD8 single-positive (SP) cells; and reducing cell surface CD5 expression. In contrast, in the Shh(-/-) thymus the ratio of CD4/CD8 cells and both positive and negative selection of a transgenic TCR were increased, demonstrating that Shh does indeed influence TCR repertoire selection and the transition from double-positive (DP) to SP cell in a physiological situation. In peripheral T cells, Gli2DeltaN(2) expression attenuated T-cell activation and proliferation, by a mechanism upstream of ERK phosphorylation.

Animals↗
PubMed1989

Developmental regulation of the extrathymic differentiation potential of the progenitor cells for T cell lineage.

Interleukin-2 (IL-2) generates T lineage cell lines (IL-3B series) directly from the isolated interleukin 3 (IL-3)-induced pluripotential progenitor colonies obtained form adult spleen in vitro. The phenomenon can be reproduced by the combined IL-3/IL-2 bulk culture system. In order to compare the differentiation potential of such progenitors in various ontogenical stages, we have established a number of cell lines from fetal livers (LFD series), fetal thymus (FTD15), newborn spleens (SED series), and adult spleens (SPB series) using the IL-3/IL-2 culture system. The phenotypes of cell lines varied depending upon the developmental stages; LFD lines, Thy1+CD3-CD4-CD8-B220+, FTD15, Thy1+CD3+CD4-CD8+B220-, and SPB and IL-3B lines, Thy1+CD3+CD4-CD8+B220+. Analysis of T cell receptor (TCR) genes revealed that all of the TCR genes (alpha, beta, gamma, and delta) were in germ line configurations in LFD lines. In LFD17 and 19, from 17 and 19 gestation days (GD) respectively, however, germ line transcripts or TCR beta gene were detected, suggesting that they were in the earliest phase of T cell commitment. In LFD14 line from GD14 fetal liver, no such transcript could be detected. In contrast, FTD15 showed complete rearrangement of every TCR gene with full-length TCR alpha and beta gene mRNA. On the other hand, all of the SED, SPB, and IL-3B series of lines exhibited the rearrangement of every TCR gene with productive TCR alpha and beta gene mRNA. The results indicated that progenitors in postnatal spleen, in contrast to those in fetal liver, had the potential to rearrange and express the TCR genes in extrathymic conditions in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Limiting dilution analysis of the stem cells for T cell lineage.

Stem cell activities of bone marrow, spleen, thymus, and fetal liver cells for T cell lineage were studied comparatively by transferring the cells from these organs through i.v. or intrathymus (i.t.) route into right leg- and tail-shielded (L-T-shielded) and 900 R-irradiated recipient mice, which were able to survive without supplying hemopoietic stem cells. Cells from B10.Thy-1.1 (H-2b, Thy-1.1) mice were serially diluted and were transferred into L-T-shielded and irradiated C57BL/6 (H-2b, Thy-1.2) mice, and 21 days later the thymus cells of recipient mice were assayed for Thy-1.1+ cells by flow cytofluorometry. The percentage of recipient mice possessing donor-type T cells was plotted against the number of cells transferred, and the stem cell activity in each cell source was expressed as the 50% positive value, the number of donor cells required for generating donor-type T cells in the thymuses of 50% of recipient mice. In i.v. transfer experiments, the activity of bone marrow cells was similar to that of fetal liver cells, and about 100 times and nearly 1000 times higher than those of spleen cells and thymus cells, respectively. In i.t. transfer experiments, the number of cells required for generating donor-type T cells was much lower than that in i.v. transfer experiments, although the ratio in 50% positive values between i.v. and i.t. transfers differed among cell sources. In i.t. transfers, the 50% positive value of bone marrow cells was five times, 400 times, and 500 times higher than that of fetal liver cells, spleen cells, and thymus cells, respectively. Our previous finding that stem cells are enriched in the spleens of mice which were whole body-irradiated and marrow-reconstituted 7 days earlier was confirmed also by the present limiting dilution assay carried out in i.v. as well as i.t. transfers.

Animals↗
PubMed1993

Hyperplastic polyps: a cell lineage which both synthesizes and secretes trefoil-peptides and has phenotypic similarity with the ulcer-associated cell lineage.

Hyperplastic polyps are common benign lesions of uncertain histogenesis, which occur in the colon in populations at risk for colorectal carcinoma. They contain neutral/MUC1 gene-related mucin which in turn is closely associated with the trefoil-peptide pS2, a major component of the ulcer-associated cell lineage, previously termed pseudopyloric metaplasia. We have examined 17 hyperplastic polyps for expression of the trefoil-peptides pS2 and human spasmolytic polypeptide by in situ hybridization and immunohistochemistry, as well as by using antisera to epidermal growth factor/urogastrone and its receptor and to epitopes of the product of the MUC1 gene to characterize any further similarity between these lesions and the ulcer-associated cell lineage and thus help elucidate the nature of the lesions. Our investigations show both human spasmolytic polypeptide and pS2 messenger RNA within the polyps, whereas only pS2 peptide could be demonstrated immunohistochemically. Epidermal growth factor/urogastrone, its receptor, and antisera to the MUC1 gene also showed widespread staining of these polyps. We suggest that hyperplastic polyps are formed of a lineage that both synthesizes and secretes trefoil-peptides and the MUC1 mucin and that hyperplastic polyps may be related to the phenotypically similar ulceration-associated cell lineage.

Cell Line↗
PubMed2005

Adeno-associated virus-mediated bone morphogenetic protein-7 gene transfer induces C2C12 cell differentiation into osteoblast lineage cells.

AIM: To investigate the effects of bone morphogenetic protein-7 (BMP7)-expressing recombinant adeno-associated virus (AAV) vector on the differentiation of C2C12 cells. METHODS: AAV-BMP7 was packaged by infecting the stable cell clone BHK-21 (integrated with recombinant AAV vector plasmid pSNAV-BMP7) with recombinant herpes simplex virus type 1, which expresses AAV-2 Rep and Cap and possesses AAV packaging functions. Following infection with AAV-BMP7 at multiplicities of infection of 1 x 10(5) vector genomes per cell and subsequent culture, C2C12 cells were assessed qualitatively for BMP7 production, alkaline phosphatase activity, osteocalcin production and Cbfal and MyoD expression. RESULTS: C2C12 cells transduced with AAV-BMP7 could produce BMP7 protein until d 28. Alkaline phosphatase in the cultured C2C12 cell lysate was elevated. Secreted osteocalcin in the culture medium was detectable at d 12 and Cbfal mRNA expression level was upregulated, coinciding with downregulation of MyoD in a temporal manner. CONCLUSION: The present in vitro study demonstrated that AAV-BMP7 could infect and efficiently convert C2C12 cells from myoblasts into osteoblast lineage cells.

Alkaline Phosphatase↗
PubMed2003

Bone marrow monocyte lineage cells adhere on injured endothelium in a monocyte chemoattractant protein-1-dependent manner and accelerate reendothelialization as endothelial progenitor cells.

Peripheral blood (PB)-derived CD14+ monocytes were shown to transdifferentiate into endothelial cell (EC) lineage cells and contribute to neovascularization. We investigated whether bone marrow (BM)- or PB-derived CD34-/CD14+ cells are involved in reendothelialization after carotid balloon injury. Although neither hematopoietic nor mesenchymal stem cells were included in human BM-derived CD34-/CD14+ monocyte lineage cells (BM-MLCs), they expressed EC-specific markers (Tie2, CD31, VE-cadherin, and endoglin) to an extent identical to mature ECs. When BM-MLCs were cultured with vascular endothelial growth factors, hematopoietic markers were drastically decreased and new EC-specific markers (Flk and CD34) were induced. BM-MLCs were intra-arterially transplanted into balloon-injured arteries of athymic nude rats. When BM-MLCs were activated by monocyte chemoattractant protein-1 (MCP-1) in vivo or in vitro, they adhered onto injured endothelium, differentiated into EC-like cells by losing hematopoietic markers, and inhibited neointimal hyperplasia. Ability to prevent neointimal hyperplasia was more efficient than that of BM-derived CD34+ cells. MCP-dependent adhesion was not observed in PB-derived CD34-/CD14+ monocytes. Regenerated endothelium exhibited a cobblestone appearance, blocked extravasation of dye, and induced NO-dependent vasorelaxation. Basal adhesive activities on HUVECs under laminar flow and beta1-integrin expression (basal and active forms) were significantly increased in BM-MLCs compared with PB-derived monocytes. MCP-1 markedly enhanced adhesive activity of BM-MLCs (2.8-fold) on HUVECs by activating beta1-integrin conformation. Thus, BM-MLCs can function as EC progenitors that are more potent than CD34+ cells and acquire the ability to adhere on injured endothelium in a MCP-1-dependent manner, leading to reendothelialization associated with inhibition of intimal hyperplasia. This will open a novel window to MCP-1-mediated biological actions and vascular regeneration strategies by cell therapy.

Angioplasty, Balloon↗
PubMed1996

In vitro differentiation of murine Sca-1+Lin- cells into myeloid, B cell and T cell lineages.

Hematopoietic progenitor cells were shown to be capable of differentiating into myeloid, B cell and T cell lineages. We used a two-step culture system in which enriched murine hematopoietic progenitors in bone marrow were first plated in viscid culture medium containing methylcellulose, erythropoietin (EPO), stem cell factor (SCF) and interleukin (IL)-7. One thousand enriched murine marrow cells formed 53.5 +/- 12.1 (mean +/- SD) primary colonies. Cells from a single blast colony were separated into two aliquots and replated in secondary methylcellulose cultures containing SCF and IL-7 for B cell lineage and SCF, IL-3, G-CSF, GM-CSF and EPO for myeloid lineage. Next, cells from five to ten primary blast colonies were cultured again in embryonal thymus (25 Gy irradiated). One aliquot of blast colonies in a primary culture contained four colony forming units (CFU) of granulocytes, erythroblasts, macrophages and megakaryocytes, eight CFU-granulocytes and macrophages, and 28 BFU-E in a representative secondary myeloid culture. Another aliquot formed a few B cell colonies (2-10) in a secondary B cell culture. B lymphoid colonies were composed of blast-like cells with B-220 antigen. T cells in a secondary T cell culture consisted of 16% L3T4+, 16% CD8+ and 11% CD3+ of bone marrow origin in the thymus. From these results, we concluded that cells in the primary colonies from Sca-1+Lin- hematopoietic stem cells could differentiate into B cell, T cell and myeloid lineages.

Animals↗
PubMed2005

Increased expression of CD27 on activated human memory B cells correlates with their commitment to the plasma cell lineage.

Plasma cells (PC) or Ig-secreting cells (ISC) are terminally differentiated B cells responsible for the production of protective Ig. ISC can be generated in vitro by culturing human B cells with the T cell-derived stimuli CD40L, IL-2, and IL-10. ISC have traditionally been identified by the increased expression of CD38, analogous to primary human PC, and the acquired ability to secrete Ig. By tracking the proliferation history of activated B cells, we previously reported that the differentiation of memory B cells into CD38(+) B cells is IL-10 dependent, and increases in frequency with cell division. However, <50% of CD38(+) cells secreted Ig, and there was a population of CD38(-) ISC. Thus, the PC phenotype of CD38(+) cells generated in vitro did not correlate with PC function. To address this, we have examined cultures of activated memory B cells to accurately identify the phenotype of ISC generated in vitro. We found that CD27 is also up-regulated on memory B cells in an IL-10-dependent and division-dependent manner, and that ISC segregated into the CD27(high) subset of activated memory B cells irrespective of the acquired expression of CD38. The ISC generated in these cultures expressed elevated levels of the transcription factors Blimp-1 and X box-binding protein-1 and reduced levels of Pax-5, and exhibited selective migration toward CXCL12, similar to primary PC. We propose that the differentiation of memory B cells into PC involves a transitional stage characterized by a CD27(high)CD38(-) phenotype with the acquired ability to secrete high levels of Ig.

ADP-ribosyl Cyclase↗
PubMed1999

Differentiation of a cell line of human cervical argyrophil small cell carcinoma to macrophage lineage cells.

To investigate the origin of argyrophil small cell carcinoma (ASCC) of the uterine cervix, we examined the influence of dibutyryl cyclic adenosine 3',5'-monophosphate (dB-cAMP), a known differentiation inducer, on the characteristics of an ASCC cell line, TC-YIK, which has been shown to be a useful in vitro experimental model of ASCC. In TC-YIK cells after treatment with dB-cAMP, two specific antigenic markers of macrophages, CD14 and human leukocyte antigen-DR, were detected by flow cytometric analysis. In addition, interferon-gamma mRNA was detected by reverse transcription-polymerase chain reaction and interferon-gamma protein was detected by ELISA. More than 90% of the cells stained positive for alpha-naphthyl butyrate esterase, 1% of the cells showed phagocytotic activity against Micrococcus lysodeikticus, and 22% of the cells had M. lysodeikticus adsorbed on their surface. Furthermore, granulocyte-macrophage colony stimulating factor accelerated the proliferation of TC-YIK cells. These results indicate that dB-cAMP promotes differentiation of ASCC cells to macrophages. In contrast, less than 10% of the cells showed stellate morphology, suggesting differentiation to neuronal cells after treatment with dB-cAMP, as reported previously. Thus, TC-YIK cells have been shown to differentiate both into macrophage lineage cells and neuronal cells, suggesting that ASCC originates from undifferentiated stem cells.

Adult↗
PubMed1984

Cell lineage analysis of Schwann cells in the PNS determined by shiverer-normal mouse chimeras.

The myelin of the peripheral nervous system from the shiverer mutant mice is characterized by the absence of myelin basic protein, while the other myelin protein components are present at normal levels. Myelin lamella formation is normal in the shiverer mutant. Therefore, by using antiserum against myelin basic protein, we can distinguish the shiverer from the wild-type control myelin immunohistochemically. To study the cell lineage of Schwann cells, chimeras produced by the aggregation of eight-cell embryos from wild-type mice and shiverer mice have been used. Using myelin basic protein as a marker, it was observed that Schwann cells in the sciatic nerve existed as patches of cells with like-genotype. The patches occurred in a linear array along the axons with some intermingling of Schwann cells. Complete randomization by intermingling of Schwann cells was not observed and clones of Schwann cells may persist as contiguous groups throughout peripheral nerve development.

Animals↗
PubMed1981

Astrocyte cell lineage. I. Astrocyte progenitor cells in mouse neopallium.

The astrocyte cell lineage during postnatal development of the neopallium of Swiss mice was studied, using a colony culture assay method in which dissociated neopallial cells form discrete colonies in culture. It was found that immature epithelial-like cells that from type A colonies in culture come primarily from the subventricular zone but also from other regions of the neopallium. In culture, cells of type A colonies from type C colonies consisting of cells, which although still epithelial like, differ morphologically from the type A colony-forming cells. In the presence of dibutyryl cyclic adenosine monophosphate (dBcAMP) the type C colonies form cells rich in glial fibrillary acidic protein (GFAP) and stainable with Cajal's gold chloride sublimate, a stain specific for astrocytes. Therefore, it is proposed that type A colony-forming cells are astrocyte progenitor cells resembling the "pale" cells found in the subventricular zone (Blakemore and Jolly, '72), the "large glioblasts" (Sturrock, '76) and the free subependymal cells (Privat, '70; Paterson et at., '73) in the corpus callosum. The sequence of the lineage, i.e., cells forming type A colonies give rise to cells forming type C colonies which eventually differentiate into astrocytes, takes place in situ as well as in culture. As postnatal development of the neopallium progresses the number of colony-forming cells decreases in the subventricular zone and in other parts of the neopallium. The astrocyte progenitor cells migrate from the subventricular zone to other parts of the neopallium and progress through the lineage of differentiation in all regions of the neopallium.

Animals↗
PubMed1993

Genetic analysis of developmental mechanisms in hydra. XXI. Enhancement of regeneration in a regeneration-deficient mutant strain by the elimination of the interstitial cell lineage.

The interstitial cell lineage, including interstitial stem cells, nerve cells, and nematocytes, was eliminated from a regeneration-deficient mutant strain (reg-16) of Hydra magnipapillata. The resultant interstitial cell lineage-free (or "epithelial") reg-16 animals showed a marked enhancement in the ability to regenerate head structures. The epithelial reg-16 polyps regenerated nearly the same number of tentacles as was originally present within 8 days after head removal, while interstitial cell lineage-containing (or "complete") reg-16 polyps restored less than one-third of their original tentacle number under the same conditions. Lateral tissue transplantation was used to examine the head activation and inhibition potentials. The gradients of the two potentials along the body axis of intact epithelial 105 (a wild-type strain) and intact epithelial reg-16 polyps were nearly identical to the gradients in their complete counterparts. The changes of the two potentials occurring after head removal in the epithelial 105 animals were also similar to those in the complete 105 animals. However, the postdecapitation changes in the epithelial reg-16 polyps were different from those in complete reg-16 polyps. The changes in the epithelial reg-16 animals were similar to those observed in wild-type hydra while those of complete reg-16 polyps were highly abnormal. These observations suggest that the phenotypic expression of the genetic defect present in the reg-16 mutant strain is attenuated when the interstitial cell lineage is eliminated from its tissue. The role of the interstitial cell lineage in head regeneration and the nature of the defect present in the reg-16 strain are discussed based on the observations made in this and previous related studies.

Animals↗
PubMed1979

A new class of cell surface antigens. Quantitative absorption studies defining cell-lineage-specific antigens on hemopoietic cells.

A new class of cell surface antigens are described which are expressed on cells within a particular differentiation pathway. These antigens, termed cell-lineage-specific antigens, are shown to be distinct from differentiation antigens and from histocompatibility antigens. The presence of these antigens was demonstrated by raising antisera against terminally differentiated hemopoietic cells such as platelets, thymocytes, and macrophages and showing cross-reaction with the pluripotent stem cells from which these cells were derived. Quantitative absorption studies of each antiserum showed the antigens to be largely cell-lineage-specific. For example, the anti-stem cell activity in anti-platelet serum was not absorbed out with thymocytes or macrophages from the same mouse strain but was removed by absorption with platelets. Absorption of each antiserum with nonhemopoietic mouse tissues such as brain, kidney, liver, and testis did not reduce anti-stem cell activity. Thus, each antiserum was shown to be tissue specific and species specific. Hemopoietic cells from mouse strains other than CBA absorbed out most of the anti-stem cell activity indicating cell-lineage-specific antigens to be common to the mouse strains tested.

Animals↗