Altered T cell differentiation and Notch signaling induced by the ectopic expression of keratin K10 in the epithelial cells of the thymus

2005 ◽  
Vol 95 (3) ◽  
pp. 543-558 ◽  
Author(s):  
Mirentxu Santos ◽  
Paula Río ◽  
Sergio Ruiz ◽  
Jesús Martínez-Palacio ◽  
Carmen Segrelles ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
T Cell ◽  
Epithelial Cells ◽  
Notch Signaling ◽  
Ectopic Expression ◽  
T Cell Differentiation

Electron microscope study of the secretory activity of epithelial cells in embryonic thymus

1990 ◽  
Vol 48 (3) ◽  
pp. 382-383
Author(s):  
H. Alasam
Keyword(s):  
Cell Differentiation ◽  
T Cell ◽  
Epithelial Cells ◽  
Electron Density ◽  
Secretory Activity ◽  
T Cell Differentiation ◽  
High Electron ◽  
Transmission Electron ◽  
Medullary Epithelial Cells ◽  
Thymic Factor

The possibility that intrathymic T-cell differentiation involves stem cell-lymphoid interactions in embryos led us to study the ultrastructure of epithelial cell in normal embryonic thymus. Studies in adult thymus showed that it produces several peptides that induce T-cell differentiation. Several of them have been chemically characterized, such as thymosin α 1, thymopoietin, thymic humoral factor or the serum thymic factor. It was suggested that most of these factors are secreted by populations of A and B-epithelial cells.Embryonic materials were obtained from inbred matings of Swiss Albino mice. Thymuses were disected from embryos 17 days old and prepared for transmission electron microscopy. Our studies showed that embryonic thymus at this stage contains undifferentiated and differentiated epithelial cells, large lymphoblasts, medium and few small lymphocytes (Fig. 5). No differences were found between cortical and medullary epithelial cells, in contrast to the findings of Van Vliet et al,. Epithelial cells were mostly of the A-type with low electron density in both cytoplasm and nucleus. However few B-type with high electron density were also found (Fig. 7).

scholarly journals The Notch signaling pathway controls CD8+ T cell differentiation independently of the classical effector HES1

PLoS ONE ◽  
2019 ◽  
Vol 14 (4) ◽  
pp. e0215012 ◽  
Author(s):  
Dave Maurice De Sousa ◽  
Frédéric Duval ◽  
Jean-François Daudelin ◽  
Salix Boulet ◽  
Nathalie Labrecque
Keyword(s):  
Cell Differentiation ◽  
T Cell ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Cd8 T Cell ◽  
Notch Signaling Pathway ◽  
T Cell Differentiation

scholarly journals Blueprint of human thymopoiesis reveals molecular mechanisms of stage-specific TCR enhancer activation

2020 ◽  
Vol 217 (9) ◽  
Author(s):  
Agata Cieslak ◽  
Guillaume Charbonnier ◽  
Melania Tesio ◽  
Eve-Lyne Mathieu ◽  
Mohamed Belhocine ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
T Cell ◽  
Molecular Mechanisms ◽  
Lymphoblastic Leukemia ◽  
Ectopic Expression ◽  
Regulatory Elements ◽  
T Cell Differentiation ◽  
Epigenetic Changes ◽  
Human T Cell ◽  
Cell Commitment

Cell differentiation is accompanied by epigenetic changes leading to precise lineage definition and cell identity. Here we present a comprehensive resource of epigenomic data of human T cell precursors along with an integrative analysis of other hematopoietic populations. Although T cell commitment is accompanied by large scale epigenetic changes, we observed that the majority of distal regulatory elements are constitutively unmethylated throughout T cell differentiation, irrespective of their activation status. Among these, the TCRA gene enhancer (Eα) is in an open and unmethylated chromatin structure well before activation. Integrative analyses revealed that the HOXA5-9 transcription factors repress the Eα enhancer at early stages of T cell differentiation, while their decommission is required for TCRA locus activation and enforced αβ T lineage differentiation. Remarkably, the HOXA-mediated repression of Eα is paralleled by the ectopic expression of homeodomain-related oncogenes in T cell acute lymphoblastic leukemia. These results highlight an analogous enhancer repression mechanism at play in normal and cancer conditions, but imposing distinct developmental constraints.

scholarly journals The Notch Signaling Pathway Controls Short-Lived Effector CD8+ T Cell Differentiation but Is Dispensable for Memory Generation

2015 ◽  
Vol 194 (12) ◽  
pp. 5654-5662 ◽  
Author(s):  
Mélissa Mathieu ◽  
Frédéric Duval ◽  
Jean-François Daudelin ◽  
Nathalie Labrecque
Keyword(s):  
Cell Differentiation ◽  
T Cell ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Cd8 T Cell ◽  
Notch Signaling Pathway ◽  
T Cell Differentiation

INDUCTION OF T-CELL DIFFERENTIATION IN VITRO BY THYMUS EPITHELIAL CELLS

1975 ◽  
Vol 249 (1 Thymus Factor) ◽  
pp. 492-498 ◽  
Author(s):  
Samuel D. Waksal ◽  
Irun R. Cohen ◽  
Harlan W. Waksal ◽  
Hartmut Wekerle ◽  
Ronald L. St. Pierre ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
T Cell ◽  
Epithelial Cells ◽  
T Cell Differentiation ◽  
Thymus Epithelial Cells

Notch Signaling in Hematopoietic Precursor Cells Maintains the Expression of Genes Required for Stem Cell Self-Renewal and Promotes the Expression of Genes Associated with T cell Differentiation.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1699-1699
Author(s):  
Keizo Kato ◽  
Barbara Varnum-Finney ◽  
Irwin D. Bernstein
Keyword(s):  
Stem Cell ◽  
Cell Differentiation ◽  
T Cell ◽  
Notch Signaling ◽  
T Cell Differentiation ◽  
The Self ◽  
Self Renewal ◽  
Notch Ligand ◽  
Expression Of Genes ◽  
Hematopoietic Precursor

Abstract Notch Signaling in Hematopoietic Precursor Cells Maintains the Expression of Genes Required for Stem Cell Self-renewal and Promotes the Expression of Genes Associated with T cell Differentiation. Keizo Kato, Barbara Varnum-Finney, Irwin D. Bernstein Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA We have previously shown that Notch signaling promotes the self-renewal of hematopoietic precursors, including short-term repopulating cells, and induces early T-cell differentiation. Here we evaluate gene expression in murine Lin-Sca-1+c-kit+ Hoechst side population (SKSP) bone marrow cells during culture with the immobilized Notch ligand, Delta1ext-IgG, consisting of the extracellular domain of Delta1 fused to the Fc domain of human-IgG1 for 28 days with SCF, IL-6, IL-11 and Flt-3-ligand. We analyzed hematopoietic stem cell (HSC) associated genes, including polycomb genes, Bmi-1 and Rae28, required for HSC self-renewal, and Rex-1 required for embryonic stem cell self-renewal, together with early T-lymphoid differentiation associated genes such as GATA-3, pre-Ta and CD3e, by semi-quantitative or real-time RT-PCR. After culture for 7 or 14 days with Delta1ext-IgG, the expression of Bmi-1, Rae28 and Rex-1 was greater in cultures containing Delta1ext-IgG compared to those without. Bmi-1, Rae28 and Rex-1 were likely not direct targets of Notch signaling since the expression in SKSP cells was equivalent after 3 hours culture in the presence or absence of Notch ligand, whereas rapid up-regulation of the direct Notch target Hes1 was observed 3 hours after incubation with Delta1ext-IgG. Expression of GATA-3, pre-Ta and CD3e was induced by Notch signaling since their expression was seen by 7-14 days with but not without Delta1ext-IgG. Furthermore, the expression of these genes was dependent on Notch signaling since removal of cells from Notch ligand after culture for 28 days led to a rapid reduction of Hes1 expression within 3 hours, and a slower reduction in genes associated with self-renewal observed after 2 days. Our results suggest that Notch signaling regulates the self-renewal of hematopoietic precursors by maintaining the expression of genes known to be required for stem cell self-renewal, while also promoting the expression of T-cell differentiation-associated genes.

Distinctive Roles of Stem Cell Factor and IL-7 in T Cell Development.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3156-3156
Author(s):  
Hongfang Wang ◽  
L. Jeanne Pierce ◽  
Gerald J. Spangrude
Keyword(s):  
Stem Cell ◽  
Cell Differentiation ◽  
T Cell ◽  
Notch Signaling ◽  
Stem Cell Factor ◽  
Critical Role ◽  
T Cell Development ◽  
Cell Development ◽  
T Cell Differentiation ◽  
Lineage Differentiation

Abstract Notch signaling plays a critical role in T lineage commitment during lymphoid differentiation. However, Notch signaling alone is not sufficient to support T cell development through the CD4/CD8 double positive (DP) stage in vitro. We here report distinct effects of several cytokines on T cell differentiation in the OP9-DL1 cell culture model. Our studies show that Flt3 ligand enhances the proliferation of progenitors but has no obvious effect on differentiation. In contrast, stem cell factor (SCF) favors the proliferation of CD4/CD8 double negative (DN) lymphoid progenitors and inhibits differentiation to the DP stage in a dose-dependent manner. Differentiation of the NK lineage is promoted under these conditions. Conversely, blocking the function of SCF that is expressed endogenously by OP9-DL1 cells inhibits proliferation of lymphoid progenitors and accelerates T lineage differentiation. IL-7 is necessary for differentiation from the DP to the CD8 single positive (SP) stage, and is also required for γδ T lineage development. We also find a dosage effect of IL-7 during T cell development. OP9 and OP9-DL1 stromal cells produce endogenous levels of IL-7 that are sufficient to support B and DP T cell differentiation. However, the amount of endogenous IL-7 is not sufficient to support T cell differentiation from the DP to the SP stage. Addition of exogenous IL-7 (1–10 ng/ml) to the cultures promotes SP differentiation, while blocking endogenous IL-7 with anti-IL-7 antibody inhibits both B and T cell development. We conclude that activation through the Notch pathway is sufficient to suppress B lineage differentiation and thereby promote T lineage commitment, but is not sufficient to promote the subsequent stages of T cell development. SCF promotes expansion and directs NK lineage differentiation at the expense of T cell development, while IL-7 provides both proliferation as well as T lineage differentiation signals. T cell development from the DN to the DP stage requires a low amount of IL-7, while differentiation from the DP to the SP stage requires a higher level of IL-7. The balance between the effects mediated by these cytokines, along with Notch signaling, plays a critical role in regulating development of the T and NK lineages.

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