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

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

Liu, Dong
•
Kousa, Anastasia, I
•
O'Neill, Kathy E.
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June 1, 2020
Development

Thymus function depends on the epithelial compartment of the thymic stroma. Cortical thymic epithelial cells (cTECs) regulate T cell lineage commitment and positive selection, while medullary (m) TECs impose central tolerance on the T cell repertoire. During thymus organogenesis, these functionally distinct sub-lineages are thought to arise from a common thymic epithelial progenitor cell (TEPC). However, the mechanisms controlling cTEC and mTEC production from the common TEPC are not understood. Here, we show that emergence of the earliest mTEC lineage-restricted progenitors requires active NOTCH signaling in progenitor TEC and that, once specified, further mTEC development is NOTCH independent. In addition, we demonstrate that persistent NOTCH activity favors maintenance of undifferentiated TEPCs at the expense of cTEC differentiation. Finally, we uncover a cross-regulatory relationship between NOTCH and FOXN1, a master regulator of TEC differentiation. These data establish NOTCH as a potent regulator of TEPC and mTEC fate during fetal thymus development, and are thus of high relevance to strategies aimed at generating/regenerating functional thymic tissue in vitro and in vivo.

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Type
research article
DOI
10.1242/dev.178582
Web of Science ID

WOS:000567372300007

Author(s)
Liu, Dong
Kousa, Anastasia, I
O'Neill, Kathy E.
Rouse, Paul
Popis, Martyna
Farley, Alison M.
Tomlinson, Simon R.
Ulyanchenko, Svetlana
Guillemot, Francois
Seymour, Philip A.
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Date Issued

2020-06-01

Published in
Development
Volume

147

Issue

12

Article Number

dev178582

Subjects

Developmental Biology

•

Developmental Biology

•

thymus

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thymic epithelial cell

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stem cell

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progenitor cell

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lineage divergence

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differentiation

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cell fate regulation

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notch signaling

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functional thymus

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stem-cells

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t-cells

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transcription factor

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lateral induction

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self-tolerance

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cross-talk

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aire

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expression

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identification

Note

This is an Open Access article distributed under the terms of the Creative Commons Attribution License.

Editorial or Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
UPRAD  
Available on Infoscience
September 24, 2020
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/171888
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