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TGF-β Signaling in Stem Cell Fate Determination

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TGF-β in Human Disease

Abstract

Stem cells, which can self-renew and can differentiate to various cell types, have great potential applications in regenerative medicine. The signaling pathways employed by TGF-β family members (including TGF-β, Activin, Nodal, BMPs, and others) are evolutionarily conserved and regulate embryogenesis and adult tissue homeostasis and repair. Disturbance of production or bioactivity of the ligands and of intracellular signal transduction elicited from TGF-β family members (generally called TGF-β signaling) can lead to various diseases, including cancer, fibrosis, and cardiovascular diseases. Consistent with their critical roles in directing normal development, TGF-β family members have been established as key extrinsic signals that regulate fate commitment in both embryonic and adult stem cells. In this chapter, we review the functions and the underlying molecular mechanisms of TGF-β family members in determining embryonic stem cell fate choices between self-renewal, commitment, and subsequent differentiation to three germ layers and their progenies. We also summarize how TGF-β-related factors control fate commitment of five extensively investigated adult stem cells—intestinal, hair follicle, neural, hematopoietic, and mesenchymal stem cells. The principles gained from these studies illustrate on how stem cell fates can be regulated by extrinsic signals and pave a road for the potential medical applications of stem cells, either as transplanted cells after ex vivo expansion or as in vivo resident stem cells activated in endogenous stem cell compartments.

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Acknowledgments

We are grateful to Bing Zhao for critical comments. The work in YGC’s lab was supported by grants from the National Natural Science Foundation of China (30930050, 30921004), and the 973 Program (2006CB943401, 2010CB833706). Work in the DH lab on stem cells was supported by grants from KU Leuven (GOA-11/012), Fund of Scientific Research-Flanders (FWO-V GA.094.11N), PhD grants from the Agency for Innovation by Science and Technology (IWT) and the Interuniversity Attraction Pole Network funding (Belspo IUAP6 and IUAP7 5-year funding cycles). This work was also partially supported by grant BIL-08/10 in the framework of Tsinghua University-KU Leuven Bilateral Scientific Cooperation.

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  1. The State Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, 100084, China

    Zhongwei Li & Ye-Guang Chen

  2. Department of Development and Regeneration, Faculty of Medicine, University of Leuven (KU Leuven), Leuven, B-3000, Belgium

    Danny Huylebroeck

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  1. Zhongwei Li
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Correspondence to Ye-Guang Chen .

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  1. , Dept Medical Biochem Microbiol, Uppsala University, Box 582, Uppsala, SE-751 23, Sweden

    Aristidis Moustakas

  2. , Interdiscip. Grad. Sch. Med. Eng., University of Yamanashi, 1110 Shimokato, Chuo, 409-3898, Yamanashi, Japan

    Keiji Miyazawa

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Li, Z., Huylebroeck, D., Chen, YG. (2013). TGF-β Signaling in Stem Cell Fate Determination. In: Moustakas, A., Miyazawa, K. (eds) TGF-β in Human Disease. Springer, Tokyo. https://doi.org/10.1007/978-4-431-54409-8_2

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