TBX3 directs cell-fate decision toward mesendoderm

Clair E. Weidgang; Ronan Russell; Purushothama R. Tata; Susanne J. Kühl; Anett Illing; Martin Müller; Qiong Lin; Cornelia Brunner; Tobias M. Boeckers; Kerstin Bauer; Apriliana E R Kartikasari; Yanchun Guo; Melanie Radenz; Christof Bernemann; Matthias Weiß; Thomas Seufferlein; Martin Zenke; Michelina Iacovino; Michael Kyba; Hans R. Schöler; Michael Kühl; Stefan Liebau; Alexander Kleger

doi:10.1016/j.stemcr.2013.08.002

TBX3 directs cell-fate decision toward mesendoderm

Clair E. Weidgang, Ronan Russell, Purushothama R. Tata, Susanne J. Kühl, Anett Illing, Martin Müller, Qiong Lin, Cornelia Brunner, Tobias M. Boeckers, Kerstin Bauer, Apriliana E R Kartikasari, Yanchun Guo, Melanie Radenz, Christof Bernemann, Matthias Weiß, Thomas Seufferlein, Martin Zenke, Michelina Iacovino, Michael Kyba, Hans R. SchölerMichael Kühl, Stefan Liebau, Alexander Kleger

Research output: Contribution to journal › Article › peer-review

65 Scopus citations

Abstract

Summary Cell-fate decisions and pluripotency are dependent on networks of key transcriptional regulators. Recent reports demonstrated additional functions of pluripotency-associated factors during early lineage commitment. The T-box transcription factor TBX3 has been implicated in regulating embryonic stem cell self-renewal and cardiogenesis. Here, we show that TBX3 is dynamically expressed during specification of the mesendoderm lineages in differentiating embryonic stem cells (ESCs) in vitro and in developing mouse and Xenopus embryos in vivo. Forced TBX3 expression in ESCs promotes mesendoderm specification by directly activating key lineage specification factors and indirectly by enhancing paracrine Nodal/Smad2 signaling. TBX3 loss-of-function analyses in the Xenopus underline its requirement for mesendoderm lineage commitment. Moreover, we uncovered a functional redundancy between TBX3 and Tbx2 during Xenopus gastrulation. Taken together, we define further facets of TBX3 actions and map TBX3 as an upstream regulator of the mesendoderm transcriptional program during gastrulation.

Original language	English (US)
Pages (from-to)	248-265
Number of pages	18
Journal	Stem Cell Reports
Volume	1
Issue number	3
DOIs	https://doi.org/10.1016/j.stemcr.2013.08.002
State	Published - Sep 10 2013

Bibliographical note

Funding Information:
The authors thank R. Köhntop, S. Fischer, and S. Seltenheim for excellent technical assistance. This study was funded by the Deutsche Forschungsgemeinschaft (DFG, KL 2544/1-1, SL BO1718/4-1, MZ Ze432/5-2), German Foundation for Heart Research (F/34/11; to A.K. and S.L.), Boehringer-Ingelheim BIU (N5 to S.L.; C1 to A.K.), Helmholtz Gesellschaft (VH-VI-510 to T.M.B. and S.L.), Else-Kröner-Fresenius-Stiftung (2011_A200; to A.K. and S.L.), BMBF (MND-Net to S.L. and T.M.B., Systar to A.K.) A.K. is indebted to the Baden-Württemberg Stiftung for the financial support of this research project by the Eliteprogramme for Postdocs.

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Weidgang, C. E., Russell, R., Tata, P. R., Kühl, S. J., Illing, A., Müller, M., Lin, Q., Brunner, C., Boeckers, T. M., Bauer, K., Kartikasari, A. E. R., Guo, Y., Radenz, M., Bernemann, C., Weiß, M., Seufferlein, T., Zenke, M., Iacovino, M., Kyba, M., ... Kleger, A. (2013). TBX3 directs cell-fate decision toward mesendoderm. Stem Cell Reports, 1(3), 248-265. https://doi.org/10.1016/j.stemcr.2013.08.002

Weidgang, CE, Russell, R, Tata, PR, Kühl, SJ, Illing, A, Müller, M, Lin, Q, Brunner, C, Boeckers, TM, Bauer, K, Kartikasari, AER, Guo, Y, Radenz, M, Bernemann, C, Weiß, M, Seufferlein, T, Zenke, M, Iacovino, M, Kyba, M, Schöler, HR, Kühl, M, Liebau, S & Kleger, A 2013, 'TBX3 directs cell-fate decision toward mesendoderm', Stem Cell Reports, vol. 1, no. 3, pp. 248-265. https://doi.org/10.1016/j.stemcr.2013.08.002

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title = "TBX3 directs cell-fate decision toward mesendoderm",

abstract = "Summary Cell-fate decisions and pluripotency are dependent on networks of key transcriptional regulators. Recent reports demonstrated additional functions of pluripotency-associated factors during early lineage commitment. The T-box transcription factor TBX3 has been implicated in regulating embryonic stem cell self-renewal and cardiogenesis. Here, we show that TBX3 is dynamically expressed during specification of the mesendoderm lineages in differentiating embryonic stem cells (ESCs) in vitro and in developing mouse and Xenopus embryos in vivo. Forced TBX3 expression in ESCs promotes mesendoderm specification by directly activating key lineage specification factors and indirectly by enhancing paracrine Nodal/Smad2 signaling. TBX3 loss-of-function analyses in the Xenopus underline its requirement for mesendoderm lineage commitment. Moreover, we uncovered a functional redundancy between TBX3 and Tbx2 during Xenopus gastrulation. Taken together, we define further facets of TBX3 actions and map TBX3 as an upstream regulator of the mesendoderm transcriptional program during gastrulation.",

author = "Weidgang, {Clair E.} and Ronan Russell and Tata, {Purushothama R.} and K{\"u}hl, {Susanne J.} and Anett Illing and Martin M{\"u}ller and Qiong Lin and Cornelia Brunner and Boeckers, {Tobias M.} and Kerstin Bauer and Kartikasari, {Apriliana E R} and Yanchun Guo and Melanie Radenz and Christof Bernemann and Matthias Wei{\ss} and Thomas Seufferlein and Martin Zenke and Michelina Iacovino and Michael Kyba and Sch{\"o}ler, {Hans R.} and Michael K{\"u}hl and Stefan Liebau and Alexander Kleger",

note = "Funding Information: The authors thank R. K{\"o}hntop, S. Fischer, and S. Seltenheim for excellent technical assistance. This study was funded by the Deutsche Forschungsgemeinschaft (DFG, KL 2544/1-1, SL BO1718/4-1, MZ Ze432/5-2), German Foundation for Heart Research (F/34/11; to A.K. and S.L.), Boehringer-Ingelheim BIU (N5 to S.L.; C1 to A.K.), Helmholtz Gesellschaft (VH-VI-510 to T.M.B. and S.L.), Else-Kr{\"o}ner-Fresenius-Stiftung (2011_A200; to A.K. and S.L.), BMBF (MND-Net to S.L. and T.M.B., Systar to A.K.) A.K. is indebted to the Baden-W{\"u}rttemberg Stiftung for the financial support of this research project by the Eliteprogramme for Postdocs. ",

year = "2013",

month = sep,

day = "10",

doi = "10.1016/j.stemcr.2013.08.002",

language = "English (US)",

volume = "1",

pages = "248--265",

journal = "Stem Cell Reports",

issn = "2213-6711",

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TY - JOUR

T1 - TBX3 directs cell-fate decision toward mesendoderm

AU - Weidgang, Clair E.

AU - Russell, Ronan

AU - Tata, Purushothama R.

AU - Kühl, Susanne J.

AU - Illing, Anett

AU - Müller, Martin

AU - Lin, Qiong

AU - Brunner, Cornelia

AU - Boeckers, Tobias M.

AU - Bauer, Kerstin

AU - Kartikasari, Apriliana E R

AU - Guo, Yanchun

AU - Radenz, Melanie

AU - Bernemann, Christof

AU - Weiß, Matthias

AU - Seufferlein, Thomas

AU - Zenke, Martin

AU - Iacovino, Michelina

AU - Kyba, Michael

AU - Schöler, Hans R.

AU - Kühl, Michael

AU - Liebau, Stefan

AU - Kleger, Alexander

N1 - Funding Information: The authors thank R. Köhntop, S. Fischer, and S. Seltenheim for excellent technical assistance. This study was funded by the Deutsche Forschungsgemeinschaft (DFG, KL 2544/1-1, SL BO1718/4-1, MZ Ze432/5-2), German Foundation for Heart Research (F/34/11; to A.K. and S.L.), Boehringer-Ingelheim BIU (N5 to S.L.; C1 to A.K.), Helmholtz Gesellschaft (VH-VI-510 to T.M.B. and S.L.), Else-Kröner-Fresenius-Stiftung (2011_A200; to A.K. and S.L.), BMBF (MND-Net to S.L. and T.M.B., Systar to A.K.) A.K. is indebted to the Baden-Württemberg Stiftung for the financial support of this research project by the Eliteprogramme for Postdocs.

PY - 2013/9/10

Y1 - 2013/9/10

N2 - Summary Cell-fate decisions and pluripotency are dependent on networks of key transcriptional regulators. Recent reports demonstrated additional functions of pluripotency-associated factors during early lineage commitment. The T-box transcription factor TBX3 has been implicated in regulating embryonic stem cell self-renewal and cardiogenesis. Here, we show that TBX3 is dynamically expressed during specification of the mesendoderm lineages in differentiating embryonic stem cells (ESCs) in vitro and in developing mouse and Xenopus embryos in vivo. Forced TBX3 expression in ESCs promotes mesendoderm specification by directly activating key lineage specification factors and indirectly by enhancing paracrine Nodal/Smad2 signaling. TBX3 loss-of-function analyses in the Xenopus underline its requirement for mesendoderm lineage commitment. Moreover, we uncovered a functional redundancy between TBX3 and Tbx2 during Xenopus gastrulation. Taken together, we define further facets of TBX3 actions and map TBX3 as an upstream regulator of the mesendoderm transcriptional program during gastrulation.

AB - Summary Cell-fate decisions and pluripotency are dependent on networks of key transcriptional regulators. Recent reports demonstrated additional functions of pluripotency-associated factors during early lineage commitment. The T-box transcription factor TBX3 has been implicated in regulating embryonic stem cell self-renewal and cardiogenesis. Here, we show that TBX3 is dynamically expressed during specification of the mesendoderm lineages in differentiating embryonic stem cells (ESCs) in vitro and in developing mouse and Xenopus embryos in vivo. Forced TBX3 expression in ESCs promotes mesendoderm specification by directly activating key lineage specification factors and indirectly by enhancing paracrine Nodal/Smad2 signaling. TBX3 loss-of-function analyses in the Xenopus underline its requirement for mesendoderm lineage commitment. Moreover, we uncovered a functional redundancy between TBX3 and Tbx2 during Xenopus gastrulation. Taken together, we define further facets of TBX3 actions and map TBX3 as an upstream regulator of the mesendoderm transcriptional program during gastrulation.

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U2 - 10.1016/j.stemcr.2013.08.002

DO - 10.1016/j.stemcr.2013.08.002

M3 - Article

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AN - SCOPUS:84883897795

SN - 2213-6711

VL - 1

SP - 248

EP - 265

JO - Stem Cell Reports

JF - Stem Cell Reports

IS - 3

ER -

TBX3 directs cell-fate decision toward mesendoderm

Abstract

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