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bioRxiv · 10.1101/823021

TGF-β signaling is critical for maintenance of the tendon cell fate

Tan, G.-K.·Pryce, B. A.·Stabio, A.·Brigande, J. V.·Wang, C.·Xia, Z.·Tufa, S. F.·Keene, D. R.·Schweitzer, R.
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Abstract

Studies of cell fate focus on specification, but little is known about maintenance of the differentiated state. We find that TGF{beta} signaling plays an essential role in maintenance of the tendon cell fate. To examine the role TGF{beta} signaling in tenocytes TGF{beta} type II receptor was targeted in the Scleraxis cell lineage. Tendon development was not disrupted in mutant embryos, but shortly after birth tenocytes lost differentiation markers and reverted to a more stem/progenitor state. Targeting of Tgfbr2 using other Cre drivers did not cause tenocyte dedifferentiation suggesting a critical significance for the spatio-temporal activity of ScxCre. Viral reintroduction of Tgfbr2 to mutants was sufficient to prevent and even rescue mutant tenocytes suggesting a continuous and cell-autonomous role for TGF{beta} signaling in cell fate maintenance. These results uncover the critical importance of molecular pathways that maintain the differentiated cell fate and a key role for TGF{beta} signaling in these processes.

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Tan, G.-K., Pryce, B. A., Stabio, A., Brigande, J. V., Wang, C., Xia, Z., Tufa, S. F., Keene, D. R., Schweitzer, R.. 2019-10-29. TGF-β signaling is critical for maintenance of the tendon cell fate. https://doi.org/10.1101/823021

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