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

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 pluri...

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Main Authors: Satya Srirama Karthik Divvela, Patrick Nell, Markus Napirei, Holm Zaehres, Jiayu Chen, Wanda Maria Gerding, Huu Phuc Nguyen, Shaorong Gao, Beate Brand-Saberi
Format: Article
Language:English
Published: MDPI AG 2019-06-01
Series:Cells
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Online Access:https://www.mdpi.com/2073-4409/8/6/529
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author Satya Srirama Karthik Divvela
Patrick Nell
Markus Napirei
Holm Zaehres
Jiayu Chen
Wanda Maria Gerding
Huu Phuc Nguyen
Shaorong Gao
Beate Brand-Saberi
author_facet Satya Srirama Karthik Divvela
Patrick Nell
Markus Napirei
Holm Zaehres
Jiayu Chen
Wanda Maria Gerding
Huu Phuc Nguyen
Shaorong Gao
Beate Brand-Saberi
author_sort Satya Srirama Karthik Divvela
collection DOAJ
description 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 <i>Math6Flag-tag</i> 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.
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spelling doaj.art-e2a76edbbf72420cb9c6aba4724ae8052023-08-02T01:28:02ZengMDPI AGCells2073-44092019-06-018652910.3390/cells8060529cells8060529bHLH Transcription Factor Math6 Antagonizes TGF-β Signalling in Reprogramming, Pluripotency and Early Cell Fate DecisionsSatya Srirama Karthik Divvela0Patrick Nell1Markus Napirei2Holm Zaehres3Jiayu Chen4Wanda Maria Gerding5Huu Phuc Nguyen6Shaorong Gao7Beate Brand-Saberi8Ruhr University Bochum, Medical Faculty, Department of Anatomy and Molecular Embryology, 44801 Bochum, GermanyRuhr University Bochum, Medical Faculty, Department of Anatomy and Molecular Embryology, 44801 Bochum, GermanyRuhr University Bochum, Medical Faculty, Department of Anatomy and Molecular Embryology, 44801 Bochum, GermanyRuhr University Bochum, Medical Faculty, Department of Anatomy and Molecular Embryology, 44801 Bochum, GermanySchool of Life Science and Technology, Tongji University, 200092 Shanghai, ChinaRuhr University Bochum, Medical Faculty, Department of Human Genetics, 44801 Bochum, GermanyRuhr University Bochum, Medical Faculty, Department of Human Genetics, 44801 Bochum, GermanySchool of Life Science and Technology, Tongji University, 200092 Shanghai, ChinaRuhr University Bochum, Medical Faculty, Department of Anatomy and Molecular Embryology, 44801 Bochum, GermanyThe 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 <i>Math6Flag-tag</i> 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.https://www.mdpi.com/2073-4409/8/6/529Atoh8Math6reprogrammingMETprimed statepluripotencymesendodermTGF beta
spellingShingle Satya Srirama Karthik Divvela
Patrick Nell
Markus Napirei
Holm Zaehres
Jiayu Chen
Wanda Maria Gerding
Huu Phuc Nguyen
Shaorong Gao
Beate Brand-Saberi
bHLH Transcription Factor Math6 Antagonizes TGF-β Signalling in Reprogramming, Pluripotency and Early Cell Fate Decisions
Cells
Atoh8
Math6
reprogramming
MET
primed state
pluripotency
mesendoderm
TGF beta
title bHLH Transcription Factor Math6 Antagonizes TGF-β Signalling in Reprogramming, Pluripotency and Early Cell Fate Decisions
title_full bHLH Transcription Factor Math6 Antagonizes TGF-β Signalling in Reprogramming, Pluripotency and Early Cell Fate Decisions
title_fullStr bHLH Transcription Factor Math6 Antagonizes TGF-β Signalling in Reprogramming, Pluripotency and Early Cell Fate Decisions
title_full_unstemmed bHLH Transcription Factor Math6 Antagonizes TGF-β Signalling in Reprogramming, Pluripotency and Early Cell Fate Decisions
title_short bHLH Transcription Factor Math6 Antagonizes TGF-β Signalling in Reprogramming, Pluripotency and Early Cell Fate Decisions
title_sort bhlh transcription factor math6 antagonizes tgf β signalling in reprogramming pluripotency and early cell fate decisions
topic Atoh8
Math6
reprogramming
MET
primed state
pluripotency
mesendoderm
TGF beta
url https://www.mdpi.com/2073-4409/8/6/529
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