Rac1 deletion causes thymic atrophy
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Rac1 deletion causes thymic atrophy. / Hunziker, Lukas; Benitah, Salvador Aznar; Aznar Benitah, Salvador; Braun, Kristin M; Jensen, Kim; McNulty, Katrina; Butler, Colin; Potton, Elspeth; Nye, Emma; Boyd, Richard; Laurent, Geoff; Glogauer, Michael; Wright, Nick A; Watt, Fiona M; Janes, Sam M.
In: PLOS ONE, Vol. 6, No. 4, 29.04.2011, p. e19292.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
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
VL - 6
SP - e19292
JO - PLoS ONE
JF - PLoS ONE
SN - 1932-6203
IS - 4
ER -
ID: 200570885