Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0110191
Title: Transcriptional repressor Tbx3 is required for the hormone-sensing cell lineage in mammary epithelium
Authors: Kunasegaran K. 
Ho V. 
Chang T.H.-.T. 
De Silva D.
Bakker M.L.
Christoffels V.M.
Pietersen A.M. 
Keywords: estrogen receptor
transcription factor
transcription factor Tbx3
unclassified drug
uvomorulin
estrogen receptor
hormone
repressor protein
T box transcription factor
Tbx3 protein, mouse
adult
animal cell
animal tissue
Article
breast development
breast epithelium
cell lineage
cell type
E cadherin gene
female
flow cytometry
gene expression
gene expression regulation
gene silencing
gene targeting
hormone sensing cell
immunofluorescence
in vivo study
mammary gland
mouse
nonhuman
protein expression
stem cell
Tbx3 gene
transcription termination
aging
animal
cytology
drug effects
epithelium cell
fluorescence
genetic transcription
growth, development and aging
metabolism
newborn
reporter gene
udder
Aging
Animals
Animals, Newborn
Cell Lineage
Epithelial Cells
Female
Fluorescence
Genes, Reporter
Hormones
Mammary Glands, Animal
Mice
Receptors, Estrogen
Repressor Proteins
T-Box Domain Proteins
Transcription, Genetic
Issue Date: 2014
Publisher: Public Library of Science
Citation: Kunasegaran K., Ho V., Chang T.H.-.T., De Silva D., Bakker M.L., Christoffels V.M., Pietersen A.M. (2014). Transcriptional repressor Tbx3 is required for the hormone-sensing cell lineage in mammary epithelium. PLoS ONE 9 (10) : e110191. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0110191
Abstract: The transcriptional repressor Tbx3 is involved in lineage specification in several tissues during embryonic development. Germ-line mutations in the Tbx3 gene give rise to Ulnar-Mammary Syndrome (comprising reduced breast development) and Tbx3 is required for mammary epithelial cell identity in the embryo. Notably Tbx3 has been implicated in breast cancer, which develops in adult mammary epithelium, but the role of Tbx3 in distinct cell types of the adult mammary gland has not yet been characterized. Using a fluorescent reporter knock-in mouse, we show that in adult virgin mice Tbx3 is highly expressed in luminal cells that express hormone receptors, and not in luminal cells of the alveolar lineage (cells primed for milk production). Flow cytometry identified Tbx3 expression already in progenitor cells of the hormone-sensing lineage and co-immunofluorescence confirmed a strict correlation between estrogen receptor (ER) and Tbx3 expression in situ. Using in vivo reconstitution assays we demonstrate that Tbx3 is functionally relevant for this lineage because knockdown of Tbx3 in primary mammary epithelial cells prevented the formation of ER+ cells, but not luminal ER- or basal cells. Interestingly, genes that are repressed by Tbx3 in other cell types, such as E-cadherin, are not repressed in hormone-sensing cells, highlighting that transcriptional targets of Tbx3 are cell type specific. In summary, we provide the first analysis of Tbx3 expression in the adult mammary gland at a single cell level and show that Tbx3 is important for the generation of hormone-sensing cells. © 2014 Kunasegaran et al.
Source Title: PLoS ONE
URI: https://scholarbank.nus.edu.sg/handle/10635/165708
ISSN: 19326203
DOI: 10.1371/journal.pone.0110191
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