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

Research output: Contribution to journal › Journal article › peer-review

Standard

Canonical Notch signaling controls the early thymic epithelial progenitor cell state and emergence of the medullary epithelial lineage in fetal thymus development. / 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; Jørgensen, Mette C; Serup, Palle; Koch, Ute; Radtke, Freddy; Blackburn, C Clare.

In: Development (Cambridge, England), Vol. 147, dev178582, 2020, p. 1-16.

Research output: Contribution to journal › Journal article › peer-review

Harvard

Liu, D, Kousa, AI, O'Neill, KE, Rouse, P, Popis, M, Farley, AM, Tomlinson, SR, Ulyanchenko, S, Guillemot, F, Seymour, PA, Jørgensen, MC, Serup, P, Koch, U, Radtke, F & Blackburn, CC 2020, 'Canonical Notch signaling controls the early thymic epithelial progenitor cell state and emergence of the medullary epithelial lineage in fetal thymus development', Development (Cambridge, England), vol. 147, dev178582, pp. 1-16. https://doi.org/10.1242/dev.178582

APA

Liu, D., Kousa, A. I., O'Neill, K. E., Rouse, P., Popis, M., Farley, A. M., Tomlinson, S. R., Ulyanchenko, S., Guillemot, F., Seymour, P. A., Jørgensen, M. C., Serup, P., Koch, U., Radtke, F., & Blackburn, C. C. (2020). Canonical Notch signaling controls the early thymic epithelial progenitor cell state and emergence of the medullary epithelial lineage in fetal thymus development. Development (Cambridge, England), 147, 1-16. [dev178582]. https://doi.org/10.1242/dev.178582

Vancouver

Liu D, Kousa AI, O'Neill KE, Rouse P, Popis M, Farley AM et al. Canonical Notch signaling controls the early thymic epithelial progenitor cell state and emergence of the medullary epithelial lineage in fetal thymus development. Development (Cambridge, England). 2020;147:1-16. dev178582. https://doi.org/10.1242/dev.178582

Author

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 ; Jørgensen, Mette C ; Serup, Palle ; Koch, Ute ; Radtke, Freddy ; Blackburn, C Clare. / Canonical Notch signaling controls the early thymic epithelial progenitor cell state and emergence of the medullary epithelial lineage in fetal thymus development. In: Development (Cambridge, England). 2020 ; Vol. 147. pp. 1-16.

Bibtex

@article{89a008841c054933ad203786d28ac122,

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

abstract = "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). The mechanisms controlling cTEC and mTEC production from the common TEPC are not however 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 TEPC 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.",

author = "Dong Liu and Kousa, {Anastasia I} and O'Neill, {Kathy E} and Paul Rouse and Martyna Popis and Farley, {Alison M} and Tomlinson, {Simon R} and Svetlana Ulyanchenko and Francois Guillemot and Seymour, {Philip A} and J{\o}rgensen, {Mette C} and Palle Serup and Ute Koch and Freddy Radtke and Blackburn, {C Clare}",

note = "{\textcopyright} 2020. Published by The Company of Biologists Ltd.",

year = "2020",

doi = "10.1242/dev.178582",

language = "English",

volume = "147",

pages = "1--16",

journal = "Development",

issn = "0950-1991",

publisher = "The Company of Biologists",

}

RIS

TY - JOUR

T1 - Canonical Notch signaling controls the early thymic epithelial progenitor cell state and emergence of the medullary epithelial lineage in fetal thymus development

AU - Liu, Dong

AU - Kousa, Anastasia I

AU - O'Neill, Kathy E

AU - Rouse, Paul

AU - Popis, Martyna

AU - Farley, Alison M

AU - Tomlinson, Simon R

AU - Ulyanchenko, Svetlana

AU - Guillemot, Francois

AU - Seymour, Philip A

AU - Jørgensen, Mette C

AU - Serup, Palle

AU - Koch, Ute

AU - Radtke, Freddy

AU - Blackburn, C Clare

PY - 2020

Y1 - 2020

N2 - 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). The mechanisms controlling cTEC and mTEC production from the common TEPC are not however 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 TEPC 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.

AB - 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). The mechanisms controlling cTEC and mTEC production from the common TEPC are not however 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 TEPC 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.

U2 - 10.1242/dev.178582

DO - 10.1242/dev.178582

M3 - Journal article

C2 - 32467237

VL - 147

SP - 1

EP - 16

JO - Development

JF - Development

SN - 0950-1991

M1 - dev178582

ER -

ID: 242364245