Tbx6 is a determinant of cardiac and neural cell fate decisions in multipotent P19CL6 cells

Svetlana Gavrilov, Thomas G. Nührenberg, Anthony W. Ashton, Chang Fu Peng, Jennifer C. Moore, Klitos Konstantinidis, Christine L. Mummery, Richard N. Kitsis

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Multipotent P19CL6 cells differentiate into cardiac myocytes or neural lineages when stimulated with dimethyl sulfoxide (DMSO) or retinoic acid (RA), respectively. Expression of the transcription factor Tbx6 was found to increase during cardiac myocyte differentiation and to decrease during neural differentiation. Overexpression of Tbx6 was not sufficient to drive P19CL6 cells to a cardiac myocyte fate or to accelerate DMSO-induced differentiation. In contrast, knockdown of Tbx6 dramatically inhibited DMSO-induced differentiation of P19CL6 cells to cardiac myocytes, as evidenced by the loss of striated muscle-specific markers and spontaneous beating. Tbx6 knockdown was also accompanied by almost complete loss of Nkx2.5, a transcription factor involved in the specification of the cardiac myocyte lineage, indicating that Nkx2.5 is downstream of Tbx6. In distinction to its positive role in cardiac myocyte differentiation, Tbx6 knockdown augmented RA-induced differentiation of P19CL6 cells to both neurons and glia, and accelerated the rate of neurite formation. Conversely, Tbx6 overexpression attenuated differentiation to neural lineages. Thus, in the P19CL6 model, Tbx6 is required for cardiac myocyte differentiation and represses neural differentiation. We propose a model in which Tbx6 is a part of a molecular switch that modulates divergent differentiation programs within a single progenitor cell.

Original languageEnglish (US)
Pages (from-to)176-184
Number of pages9
JournalDifferentiation
Volume84
Issue number2
DOIs
StatePublished - Sep 2012

Fingerprint

Cardiac Myocytes
Dimethyl Sulfoxide
Tretinoin
Cell Differentiation
Transcription Factors
Striated Muscle
Neurites
Neuroglia
Stem Cells
Neurons

Keywords

  • Cardiac myocyte
  • Differentiation
  • Neuron/glial cells
  • P19CL6 cells
  • Tbx6

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology
  • Molecular Biology
  • Cancer Research

Cite this

Gavrilov, S., Nührenberg, T. G., Ashton, A. W., Peng, C. F., Moore, J. C., Konstantinidis, K., ... Kitsis, R. N. (2012). Tbx6 is a determinant of cardiac and neural cell fate decisions in multipotent P19CL6 cells. Differentiation, 84(2), 176-184. https://doi.org/10.1016/j.diff.2012.04.007

Tbx6 is a determinant of cardiac and neural cell fate decisions in multipotent P19CL6 cells. / Gavrilov, Svetlana; Nührenberg, Thomas G.; Ashton, Anthony W.; Peng, Chang Fu; Moore, Jennifer C.; Konstantinidis, Klitos; Mummery, Christine L.; Kitsis, Richard N.

In: Differentiation, Vol. 84, No. 2, 09.2012, p. 176-184.

Research output: Contribution to journalArticle

Gavrilov, S, Nührenberg, TG, Ashton, AW, Peng, CF, Moore, JC, Konstantinidis, K, Mummery, CL & Kitsis, RN 2012, 'Tbx6 is a determinant of cardiac and neural cell fate decisions in multipotent P19CL6 cells', Differentiation, vol. 84, no. 2, pp. 176-184. https://doi.org/10.1016/j.diff.2012.04.007
Gavrilov S, Nührenberg TG, Ashton AW, Peng CF, Moore JC, Konstantinidis K et al. Tbx6 is a determinant of cardiac and neural cell fate decisions in multipotent P19CL6 cells. Differentiation. 2012 Sep;84(2):176-184. https://doi.org/10.1016/j.diff.2012.04.007
Gavrilov, Svetlana ; Nührenberg, Thomas G. ; Ashton, Anthony W. ; Peng, Chang Fu ; Moore, Jennifer C. ; Konstantinidis, Klitos ; Mummery, Christine L. ; Kitsis, Richard N. / Tbx6 is a determinant of cardiac and neural cell fate decisions in multipotent P19CL6 cells. In: Differentiation. 2012 ; Vol. 84, No. 2. pp. 176-184.
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