scholarly journals NOTCH1 signaling establishes the medullary thymic epithelial cell progenitor pool during mouse fetal development

2019 ◽  
Author(s):  
Jie Li ◽  
Julie Gordon ◽  
Edward L. Y. Chen ◽  
Luying Wu ◽  
Juan Carlos Zúñiga-Pflücker ◽  
...  
Keyword(s):  
T Cell ◽  
Epithelial Cell ◽  
Notch Signaling ◽  
Cell Lineage ◽  
Lineage Tracing ◽  
Thymic Epithelial Cell ◽  
Self Tolerance ◽  
Medullary Thymic Epithelial Cell ◽  
History Of ◽  
Lineage Analysis

AbstractThe cortical and medullary thymic epithelial cell (cTEC and mTEC) lineages are essential for inducing T cell lineage commitment, T cell positive selection and the establishment of self-tolerance, but the mechanisms controlling their fetal specification and differentiation are poorly understood. Here, we show that Notch signaling is required to specify and expand the mTEC lineage. Notch1 is expressed by and active in TEC progenitors. Deletion of Notch1 in TECs resulted in depletion of mTEC progenitors and dramatic reductions in mTECs during fetal stages, consistent with defects in mTEC specification and progenitor expansion. Conversely, forced Notch signaling in all TEC resulted in widespread expression of mTEC progenitor markers and profound defects in TEC differentiation. In addition, lineage-tracing analysis indicated that all mTECs have a history of receiving a Notch signal, consistent with Notch signaling occurring in mTEC progenitors. Interestingly, this lineage analysis also showed that cTECs are divided between Notch lineage-positive and lineage-negative populations, identifying a previously unknown complexity in the cTEC lineage.

Author response for "A novel method to identify Post‐Aire stages of medullary thymic epithelial cell differentiation"

2020 ◽  
Author(s):  
Pedro Ferreirinha ◽  
Camila Ribeiro ◽  
Junko Morimoto ◽  
Jonathan J. M. Landry ◽  
Minoru Matsumoto ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Epithelial Cell ◽  
Author Response ◽  
Thymic Epithelial Cell ◽  
Epithelial Cell Differentiation ◽  
Medullary Thymic Epithelial Cell ◽  
Novel Method

scholarly journals Isolation and Characterization of Proinsulin-Producing Medullary Thymic Epithelial Cell Clones

Diabetes ◽  
2006 ◽  
Vol 55 (9) ◽  
pp. 2595-2601 ◽  
Author(s):  
Michael O. Palumbo ◽  
Dina Levi ◽  
Aziz Alami Chentoufi ◽  
Constantin Polychronakos
Keyword(s):  
Epithelial Cell ◽  
Thymic Epithelial Cell ◽  
Isolation And Characterization ◽  
Cell Clones ◽  
Medullary Thymic Epithelial Cell

scholarly journals Establishment of signaling interactions with cellular resolution for every cell cycle of embryogenesis

2018 ◽  
Author(s):  
Long Chen ◽  
Vincy Wing Sze Ho ◽  
Ming-Kin Wong ◽  
Xiaotai Huang ◽  
Lu-yan Chan ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Notch Signaling ◽  
Cell Lineage ◽  
Cellular Interaction ◽  
Cell Contact ◽  
Contact Map ◽  
C Elegans ◽  
Cellular Resolution ◽  
Signaling Interactions ◽  
Lineage Analysis

AbstractIntercellular signaling interaction plays a key role in breaking fate symmetry during animal development. Identification of the signaling interaction at cellular resolution is technically challenging, especially in a developing embryo. Here we develop a platform that allows automated inference and validation of signaling interaction for every cell cycle of C. elegans embryogenesis. This is achieved by generation of a systems-level cell contact map that consists of 1,114 highly confident intercellular contacts by modeling analysis and is validated through cell membrane labeling coupled with cell lineage analysis. We apply the map to identify cell pairs between which a Notch signaling interaction takes place. By generating expression patterns for two ligands and two receptors of Notch signaling pathway with cellular resolution using automated expression profiling technique, we are able to refine existing and identify novel Notch interactions during C. elegans embryogenesis. Targeted cell ablation followed by cell lineage analysis demonstrates the roles of signaling interactions over cell division in breaking fate symmetry. We finally develop a website that allows online access to the cell-cell contact map for mapping of other signaling interaction in the community. The platform can be adapted to establish cellular interaction from any other signaling pathways.

scholarly journals NOTCH1 signaling establishes the medullary thymic epithelial cell progenitor pool during mouse fetal development

Development ◽  
2020 ◽  
Vol 147 (12) ◽  
pp. dev178988
Author(s):  
Jie Li ◽  
Julie Gordon ◽  
Edward L. Y. Chen ◽  
Shiyun Xiao ◽  
Luying Wu ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Fetal Development ◽  
Thymic Epithelial Cell ◽  
Notch1 Signaling ◽  
Medullary Thymic Epithelial Cell

scholarly journals Aire Disruption Influences the Medullary Thymic Epithelial Cell Transcriptome and Interaction With Thymocytes

2018 ◽  
Vol 9 ◽  
Author(s):  
Cesar A. Speck-Hernandez ◽  
Amanda F. Assis ◽  
Rafaela F. Felicio ◽  
Larissa Cotrim-Sousa ◽  
Nicole Pezzi ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Thymic Epithelial Cell ◽  
Medullary Thymic Epithelial Cell ◽  
Cell Transcriptome

scholarly journals Lineage Tracing and Cell Ablation Identify a Post-Aire-Expressing Thymic Epithelial Cell Population

Cell Reports ◽  
2013 ◽  
Vol 5 (1) ◽  
pp. 166-179 ◽  
Author(s):  
Todd C. Metzger ◽  
Imran S. Khan ◽  
James M. Gardner ◽  
Maria L. Mouchess ◽  
Kellsey P. Johannes ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Cell Population ◽  
Lineage Tracing ◽  
Thymic Epithelial Cell ◽  
Cell Ablation ◽  
Epithelial Cell Population

scholarly journals Existence of a pool of T-lymphocyte colony-forming cells (T-CFC) in human bone marrow and their place in the differentiation of the T- lymphocyte lineage

Blood ◽  
1981 ◽  
Vol 58 (5) ◽  
pp. 911-915 ◽  
Author(s):  
F Triebel ◽  
WA Robinson ◽  
AR Hayward ◽  
PG Goube de Laforest
Keyword(s):  
Bone Marrow ◽  
T Cell ◽  
T Lymphocyte ◽  
Cell Lineage ◽  
Marrow Graft ◽  
In Vitro Proliferation ◽  
Complement Dependent Cytotoxicity ◽  
Self Tolerance ◽  
Proliferation And Differentiation

Abstract The existence and characteristics of bone marrow T-cell progenitors have not yet been established in man. Several pieces of evidence such as the reconstitution of certain immunodeficiencies by bone marrow graft suggest that T-cell precursors are present in the bone marrow. We report the growth of T-cell colonies from bone marrow populations using PHA-stimulated lymphocyte-conditioned medium containing T-cell growth factor (TCGF). Rosetting experiments and complement-dependent cytotoxicity assays with monoclonal antibodies indicate that the bone marrow T colony-forming cells (T-CFC) are E- OKT 3- and la+, i.e., immature progenitors. The colonies derived from these cells have the phenotype of mature T cells: E + OKT 3 + la- with either helper (OKT 4+) and suppressor (OKT 8 +) antigens. These results suggest that a thymic microenvironment may not be necessary for the in vitro proliferation and differentiation of the T-cell lineage in adult humans. These methodologies may permit direct investigation of early phenomena concerning the T-cell lineage, such as the acquisition of self-tolerance, the formation of a repertoire of specificities, and the HLA restriction phenomena that we believe takes place before the thymic maturation.

scholarly journals The Early Postnatal Life: A Dynamic Period in Thymic Epithelial Cell Differentiation

2021 ◽  
Vol 12 ◽  
Author(s):  
Ruben G. R. Pinheiro ◽  
Nuno L. Alves
Keyword(s):  
T Cells ◽  
T Cell ◽  
Epithelial Cell ◽  
T Cell Development ◽  
Thymic Epithelial Cells ◽  
Thymic Epithelial Cell ◽  
Postnatal Life ◽  
Functionally Diverse ◽  
Redundant Role

The microenvironments formed by cortical (c) and medullary (m) thymic epithelial cells (TECs) play a non-redundant role in the generation of functionally diverse and self-tolerant T cells. The role of TECs during the first weeks of the murine postnatal life is particularly challenging due to the significant augment in T cell production. Here, we critically review recent studies centered on the timely coordination between the expansion and maturation of TECs during this period and their specialized role in T cell development and selection. We further discuss how aging impacts on the pool of TEC progenitors and maintenance of functionally thymic epithelial microenvironments, and the implications of these chances in the capacity of the thymus to sustain regular thymopoiesis throughout life.

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