Rac1 deletion causes thymic atrophy

Lukas Hunziker; Salvador Aznar Benitah; Salvador Aznar Benitah; Kristin M Braun; Kim Jensen; Katrina McNulty; Colin Butler; Elspeth Potton; Emma Nye; Richard Boyd; Geoff Laurent; Michael Glogauer; Nick A Wright; Fiona M Watt; Sam M Janes

doi:10.1371/journal.pone.0019292

Rac1 deletion causes thymic atrophy

Lukas Hunziker, Salvador Aznar Benitah, Salvador Aznar Benitah, Kristin M Braun, Kim Jensen, Katrina McNulty, Colin Butler, Elspeth Potton, Emma Nye, Richard Boyd, Geoff Laurent, Michael Glogauer, Nick A Wright, Fiona M Watt, Sam M Janes

6 Citationer (Scopus)

Abstract

The thymic stroma supports T lymphocyte development and consists of an epithelium maintained by thymic epithelial progenitors. The molecular pathways that govern epithelial homeostasis are poorly understood. Here we demonstrate that deletion of Rac1 in Keratin 5/Keratin 14 expressing embryonic and adult thymic epithelial cells leads to loss of the thymic epithelial compartment. Rac1 deletion led to an increase in c-Myc expression and a generalized increase in apoptosis associated with a decrease in thymic epithelial proliferation. Our results suggest Rac1 maintains the epithelial population, and equilibrium between Rac1 and c-Myc may control proliferation, apoptosis and maturation of the thymic epithelial compartment. Understanding thymic epithelial maintenance is a step toward the dual goals of in vitro thymic epithelial cell culture and T cell differentiation, and the clinical repair of thymic damage from graft-versus-host-disease, chemotherapy or irradiation.

Originalsprog	Engelsk
Tidsskrift	PLOS ONE
Vol/bind	6
Udgave nummer	4
Sider (fra-til)	e19292
ISSN	1932-6203
DOI	https://doi.org/10.1371/journal.pone.0019292
Status	Udgivet - 29 apr. 2011
Udgivet eksternt	Ja

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10.1371/journal.pone.0019292

journal.pone.0019292&type=printableForlagets udgivne version, 6,37 MBLicens: CC BY

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title = "Rac1 deletion causes thymic atrophy",

abstract = "The thymic stroma supports T lymphocyte development and consists of an epithelium maintained by thymic epithelial progenitors. The molecular pathways that govern epithelial homeostasis are poorly understood. Here we demonstrate that deletion of Rac1 in Keratin 5/Keratin 14 expressing embryonic and adult thymic epithelial cells leads to loss of the thymic epithelial compartment. Rac1 deletion led to an increase in c-Myc expression and a generalized increase in apoptosis associated with a decrease in thymic epithelial proliferation. Our results suggest Rac1 maintains the epithelial population, and equilibrium between Rac1 and c-Myc may control proliferation, apoptosis and maturation of the thymic epithelial compartment. Understanding thymic epithelial maintenance is a step toward the dual goals of in vitro thymic epithelial cell culture and T cell differentiation, and the clinical repair of thymic damage from graft-versus-host-disease, chemotherapy or irradiation.",

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author = "Lukas Hunziker and Benitah, {Salvador Aznar} and {Aznar Benitah}, Salvador and Braun, {Kristin M} and Kim Jensen and Katrina McNulty and Colin Butler and Elspeth Potton and Emma Nye and Richard Boyd and Geoff Laurent and Michael Glogauer and Wright, {Nick A} and Watt, {Fiona M} and Janes, {Sam M}",

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T1 - Rac1 deletion causes thymic atrophy

AU - Hunziker, Lukas

AU - Benitah, Salvador Aznar

AU - Aznar Benitah, Salvador

AU - Braun, Kristin M

AU - Jensen, Kim

AU - McNulty, Katrina

AU - Butler, Colin

AU - Potton, Elspeth

AU - Nye, Emma

AU - Boyd, Richard

AU - Laurent, Geoff

AU - Glogauer, Michael

AU - Wright, Nick A

AU - Watt, Fiona M

AU - Janes, Sam M

PY - 2011/4/29

Y1 - 2011/4/29

N2 - The thymic stroma supports T lymphocyte development and consists of an epithelium maintained by thymic epithelial progenitors. The molecular pathways that govern epithelial homeostasis are poorly understood. Here we demonstrate that deletion of Rac1 in Keratin 5/Keratin 14 expressing embryonic and adult thymic epithelial cells leads to loss of the thymic epithelial compartment. Rac1 deletion led to an increase in c-Myc expression and a generalized increase in apoptosis associated with a decrease in thymic epithelial proliferation. Our results suggest Rac1 maintains the epithelial population, and equilibrium between Rac1 and c-Myc may control proliferation, apoptosis and maturation of the thymic epithelial compartment. Understanding thymic epithelial maintenance is a step toward the dual goals of in vitro thymic epithelial cell culture and T cell differentiation, and the clinical repair of thymic damage from graft-versus-host-disease, chemotherapy or irradiation.

AB - The thymic stroma supports T lymphocyte development and consists of an epithelium maintained by thymic epithelial progenitors. The molecular pathways that govern epithelial homeostasis are poorly understood. Here we demonstrate that deletion of Rac1 in Keratin 5/Keratin 14 expressing embryonic and adult thymic epithelial cells leads to loss of the thymic epithelial compartment. Rac1 deletion led to an increase in c-Myc expression and a generalized increase in apoptosis associated with a decrease in thymic epithelial proliferation. Our results suggest Rac1 maintains the epithelial population, and equilibrium between Rac1 and c-Myc may control proliferation, apoptosis and maturation of the thymic epithelial compartment. Understanding thymic epithelial maintenance is a step toward the dual goals of in vitro thymic epithelial cell culture and T cell differentiation, and the clinical repair of thymic damage from graft-versus-host-disease, chemotherapy or irradiation.

KW - Animals

KW - Atrophy

KW - Cell Proliferation

KW - Crosses, Genetic

KW - Flow Cytometry

KW - Gene Deletion

KW - Gene Expression Regulation

KW - Green Fluorescent Proteins/metabolism

KW - Heterozygote

KW - Homeostasis

KW - Kidney/embryology

KW - Mice

KW - Microscopy, Fluorescence/methods

KW - Neuropeptides/genetics

KW - Promoter Regions, Genetic

KW - Thymus Gland/embryology

KW - Time Factors

KW - rac GTP-Binding Proteins/genetics

KW - rac1 GTP-Binding Protein

U2 - 10.1371/journal.pone.0019292

DO - 10.1371/journal.pone.0019292

M3 - Journal article

C2 - 21559396

SN - 1932-6203

VL - 6

SP - e19292

JO - PLoS Computational Biology

JF - PLoS Computational Biology

IS - 4

ER -

Rac1 deletion causes thymic atrophy

Abstract

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