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bHLH Transcription Factor Math6 Antagonizes TGF-β Signalling in Reprogramming, Pluripotency and Early Cell Fate Decisions

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Ruhr University Bochum, Medical Faculty, Department of Anatomy and Molecular Embryology, 44801 Bochum, Germany
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School of Life Science and Technology, Tongji University, 200092 Shanghai, China
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Leibniz Institut für Arbeitsforschung, Technische Universität Dortmund, 44139 Dortmund, Germany
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Ruhr University Bochum, Medical Faculty, Department of Human Genetics, 44801 Bochum, Germany
*
Author to whom correspondence should be addressed.
Cells 2019, 8(6), 529; https://doi.org/10.3390/cells8060529
Received: 21 March 2019 / Revised: 30 May 2019 / Accepted: 1 June 2019 / Published: 2 June 2019
(This article belongs to the Section Stem Cells)
The basic helix-loop-helix (bHLH) transcription factor Math6 (Atonal homolog 8; Atoh8) plays a crucial role in a number of cellular processes during embryonic development, iron metabolism and tumorigenesis. We report here on its involvement in cellular reprogramming from fibroblasts to induced pluripotent stem cells, in the maintenance of pluripotency and in early fate decisions during murine development. Loss of Math6 disrupts mesenchymal-to-epithelial transition during reprogramming and primes pluripotent stem cells towards the mesendodermal fate. Math6 can thus be considered a regulator of reprogramming and pluripotent stem cell fate. Additionally, our results demonstrate the involvement of Math6 in SMAD-dependent TGF beta signalling. We furthermore monitor the presence of the Math6 protein during these developmental processes using a newly generated Math6Flag-tag mouse. Taken together, our results suggest that Math6 counteracts TGF beta signalling and, by this, affects the initiating step of cellular reprogramming, as well as the maintenance of pluripotency and early differentiation. View Full-Text
Keywords: Atoh8; Math6; reprogramming; MET; primed state; pluripotency; mesendoderm; TGF beta Atoh8; Math6; reprogramming; MET; primed state; pluripotency; mesendoderm; TGF beta
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Divvela, S.S.K.; Nell, P.; Napirei, M.; Zaehres, H.; Chen, J.; Gerding, W.M.; Nguyen, H.P.; Gao, S.; Brand-Saberi, B. bHLH Transcription Factor Math6 Antagonizes TGF-β Signalling in Reprogramming, Pluripotency and Early Cell Fate Decisions. Cells 2019, 8, 529.

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