Transcriptional repressor Tbx3 is required for the hormone-sensing cell lineage in mammary epithelium

Autor: Martijn L. Bakker, Vincent M. Christoffels, Kamini Kunasegaran, Duvini De Silva, Victor Ho, Ted H-. T. Chang, Alexandra M Pietersen
Přispěvatelé: Amsterdam Cardiovascular Sciences, General Paediatrics, Amsterdam Reproduction & Development (AR&D), Medical Biology
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Aging
Transcription
Genetic
Organogenesis
Mammary gland
lcsh:Medicine
Gene Expression
Estrogen receptor
Biochemistry
Mammary Gland Development
Mice
Genes
Reporter
Animal Cells
Breast Tumors
Medicine and Health Sciences
lcsh:Science
Multidisciplinary
Stem Cells
Animal Models
Adult Stem Cells
medicine.anatomical_structure
Receptors
Estrogen
Oncology
Mammary Epithelium
Female
Cellular Types
Stem cell
Research Article
Cell type
Lineage (genetic)
Mouse Models
Biology
Research and Analysis Methods
Fluorescence
Mammary Glands
Animal
Model Organisms
DNA-binding proteins
Breast Cancer
Genetics
medicine
Animals
Cell Lineage
Gene Regulation
Progenitor cell
Reporter gene
Biology and life sciences
lcsh:R
Proteins
Cancers and Neoplasms
Epithelial Cells
Cell Biology
Molecular biology
Hormones
Gland Development
Repressor Proteins
Animals
Newborn
lcsh:Q
T-Box Domain Proteins
Organism Development
Transcription Factors
Developmental Biology
Zdroj: PLoS ONE
PLoS ONE, Vol 9, Iss 10, p e110191 (2014)
PLoS ONE, 9(10). Public Library of Science
DOI: 10.1371/journal.pone.0110191
Popis: 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.
Databáze: OpenAIRE
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