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Canonical Notch signaling controls the early thymic epithelial progenitor cell state and emergence of the medullary epithelia lineage in fetal thymus development

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Stromal Notch ligands foster lymphopenia-driven functional plasticity and homeostatic proliferation of naive B cells

Freddy Radtke, Ute Koch

In lymphopenic environments, secondary lymphoid organs regulate the size of B and T cell compartments by supporting the homeostatic proliferation of mature lymphocytes. The molecular mechanisms underlying these responses and their functional consequences r ...

AMER SOC CLINICAL INVESTIGATION INC2022

In humans, mice, and other mammals key internal organs such as the gut, the lungs, the pancreas, and the liver all derive from the same embryonic tissue: the endoderm. The development of all of these structures thus depends on a same set of early cells, an ...

EPFL2022

Notch1 receptor signaling is essential for T cell fate specification and physiological thymic T lymphocyte development. Its dysregulation and oncogenic activation are detected in almost 80% of pediatric patients suffering from T cell acute lymphoblastic le ...

EPFL2021

Bone marrow transplantation is a well-established medical procedure for the treatment of various hematologic diseases. However, the relatively low number of hematopoietic stem cells (HSCs) that can be harvested, especially from umbilical cord blood, limits ...

EPFL2019

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Thymocytes must pass both positive and negative selections to become mature T cells. Negative selection purges thymocytes whose T-cell receptors (TCR) exhibit high affinity to self-peptide MHC complexes (self pMHC) to avoid autoimmune diseases, while posit ...

Nature Publishing Group2017

Most papers related to thymus focus on the cortical and medullary epithelial cells whereas the subcapsular layer is ignored. In this thesis, we are providing new informations about the subcapsular thymic epithelial cells (TECs) by comparing them to cortica ...

EPFL2017

Nuclear receptor corepressor 1 (NCOR1) is a transcriptional regulator bridging repressive chromatin modifying enzymes with transcription factors. NCOR1 regulates many biological processes, however its role in T cells is not known. Here we show that Cd4-Cre ...

Nature Publishing Group2017

A balancing act between stratification and EMT in cultured human thymic epithelial cells

Matteo Pluchinotta

The thymus is the primary organ for T cell differentiation and maturation. Its stroma forms a characteristic sponge-like 3D structure mainly composed of thymic epithelial cells. Despite of this unconventional epithelial architecture, TECs express markers a ...

EPFL2016

The chromatin remodeller Chd7 and the calcium ATPase Serca2 - adding new facets to the role of Notch in Hematopoiesis and T-ALL

Monique Coersmeyer

Project I: Chd7 Deficiency does not affect N1-driven T-ALL Induction and Maintenance nor impair Hematopoiesis Notch1 has been shown to be a key driver in pediatric T-cell acute lymphobastic leukemia (T-ALL). Previous work in the lab identified the chromati ...

EPFL2015

DL4-mediated Notch signaling is required for the development of fetal alpha beta and gamma delta T cells

Freddy Radtke, Ute Koch, Stéphanie Claudinot

T-cell development depends upon interactions between thymocytes and thymic epithelial cells (TECs). The engagement of delta-like 4 (DL4) on TECs by Notch1 expressed by blood-borne BM-derived precursors is essential for T-cell commitment in the adult thymus ...

Wiley-Blackwell2013