Smad7 enables STAT3 activation and promotes pluripotency independent of TGF-β signaling
Abstract
TGF-β and related growth factors critically regulate cell potency and functions. Smad7 is induced by TGF-βs and inhibits the physiological functions of TGF-β signaling. This study describes an unexpected finding that Smad7 promotes self-renewal of embryonic stem cells (ESCs) in a manner independent of its inhibition on TGF-β signaling. Instead, Smad7 acts to induce activation of transcription factor signal transducers and activators of transcription 3 (STAT3) in ESCs. Smad7 activates STAT3 through its direct binding to the cytokine receptor upstream of STAT3 activation. In agreement with the role of STAT3 in maintaining ESC pluripotency, Smad7 promotes ESC self-renewal and induced pluripotent stem cell reprogramming. This finding illustrates a regulatory mechanism for Smad7 in maintaining pluripotency, and likely in cancer and inflammation.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Sep 05, 2017
- Source ID
- 10.1073/pnas.1705755114
Entities
People
- Bin Zhao
- Chen Ding
- Chuang Sun
- Dewei Xu
- Fenfang Chen
- Jun Qin
- Lei Wang
- Mu Xiao
- Pinglong Xu
- Sheng Ye
- Shuchen Gu
- Wenjian Li
- Xia Lin
- Xin-Hua Feng
- Ye Li
- Ye-guang Chen
- Yi Li
- Yi Yu
- Zongping Xia
Organizations
- Baylor College of Medicine
- Fudan University
- Ministry of Science and Technology of the People's Republic of China
- National Institutes of Health
- National Natural Science Foundation of China
- Tsinghua University
- United States Department of Defense
- Zhejiang University