title: A Dynamic Role of TBX3 in the Pluripotency Circuitry.
abstract: Pluripotency represents a cell state comprising a fine-tuned pattern of transcription factor activity required for embryonic stem cell (ESC) self-renewal. TBX3 is the earliest expressed member of the T-box transcription factor family and is involved in maintenance and induction of pluripotency. Hence, TBX3 is believed to be a key member of the pluripotency circuitry, with loss of TBX3 coinciding with loss of pluripotency. We report a dynamic expression of TBX3 in vitro and in vivo using genetic reporter tools tracking TBX3 expression in mouse ESCs (mESCs). Low TBX3 levels are associated with reduced pluripotency, resembling the more mature epiblast. Notably, TBX3-low cells maintain the intrinsic capability to switch to a TBX3-high state and vice versa. Additionally, we show TBX3 to be dispensable for induction and maintenance of naive pluripotency as well as for germ cell development. These data highlight novel facets of TBX3 action in mESCs.
authors.affiliation: Department of Internal Medicine I, Ulm University, 89081 Ulm, Germany.
authors.forename: Ronan
authors.initials: R
authors.lastname: Russell
authors.affiliation: Department of Internal Medicine I, Ulm University, 89081 Ulm, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Ilg
authors.affiliation: Department of Cell Biology, Institute for Biomedical Engineering, Medical Faculty, RWTH Aachen University, 52074 Aachen, Germany.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Lin
authors.affiliation: Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, 48149 Münster, Germany.
authors.forename: Guangming
authors.initials: G
authors.lastname: Wu
authors.affiliation: Department of Internal Medicine I, Ulm University, 89081 Ulm, Germany.
authors.forename: André
authors.initials: A
authors.lastname: Lechel
authors.affiliation: Department of Internal Medicine I, Ulm University, 89081 Ulm, Germany.
authors.forename: Wendy
authors.initials: W
authors.lastname: Bergmann
authors.affiliation: Department of Internal Medicine I, Ulm University, 89081 Ulm, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Eiseler
authors.affiliation: Institute of Neuroanatomy, Eberhard Karls University Tübingen, 72074 Tübingen, Germany.
authors.forename: Leonhard
authors.initials: L
authors.lastname: Linta
authors.affiliation: Weis Center for Research, Geisinger Clinic, Danville, PA 17822, USA.
authors.forename: Pavan
authors.initials: P
authors.lastname: Kumar P
authors.affiliation: Institute of Neuroanatomy, Eberhard Karls University Tübingen, 72074 Tübingen, Germany.
authors.forename: Moritz
authors.initials: M
authors.lastname: Klingenstein
authors.affiliation: Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, 48149 Münster, Germany.
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Adachi
authors.affiliation: Department of Internal Medicine I, Ulm University, 89081 Ulm, Germany.
authors.forename: Meike
authors.initials: M
authors.lastname: Hohwieler
authors.affiliation: Core Facility Transgenic Mice, Ulm University, 89081 Ulm, Germany.
authors.forename: Olena
authors.initials: O
authors.lastname: Sakk
authors.affiliation: Institute of Neuroanatomy, Eberhard Karls University Tübingen, 72074 Tübingen, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Raab
authors.affiliation: Weis Center for Research, Geisinger Clinic, Danville, PA 17822, USA.
authors.forename: Anne
authors.initials: A
authors.lastname: Moon
authors.affiliation: Department of Cell Biology, Institute for Biomedical Engineering, Medical Faculty, RWTH Aachen University, 52074 Aachen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Zenke
authors.affiliation: Department of Internal Medicine I, Ulm University, 89081 Ulm, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Seufferlein
authors.affiliation: Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, 48149 Münster, Germany.
authors.forename: Hans R
authors.initials: HR
authors.lastname: Schöler
authors.affiliation: Department of Internal Medicine I, Ulm University, 89081 Ulm, Germany.
authors.forename: Anett
authors.initials: A
authors.lastname: Illing
authors.affiliation: Institute of Neuroanatomy, Eberhard Karls University Tübingen, 72074 Tübingen, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Liebau
authors.affiliation: Department of Internal Medicine I, Ulm University, 89081 Ulm, Germany. Electronic address: alexander.kleger@uni-ulm.de.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kleger
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D065150:Cellular Reprogramming; D017353:Gene Deletion; D051379:Mice; D000066450:Mouse Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*
chemical_list: D020825:T-Box Domain Proteins; C491460:Tbx3 protein, mouse