Title |
Long-term self-renewing human epicardial cells generated from pluripotent stem cells under defined xeno-free conditions
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Published in |
Nature Biomedical Engineering, December 2016
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DOI | 10.1038/s41551-016-0003 |
Pubmed ID | |
Authors |
Xiaoping Bao, Xiaojun Lian, Timothy A. Hacker, Eric G. Schmuck, Tongcheng Qian, Vijesh J. Bhute, Tianxiao Han, Mengxuan Shi, Lauren Drowley, Alleyn T. Plowright, Qing-Dong Wang, Marie-Jose Goumans, Sean P. Palecek |
Abstract |
The epicardium contributes both multi-lineage descendants and paracrine factors to the heart during cardiogenesis and cardiac repair, underscoring its potential for cardiac regenerative medicine. Yet little is known about the cellular and molecular mechanisms that regulate human epicardial development and regeneration. Here, we show that the temporal modulation of canonical Wnt signaling is sufficient for epicardial induction from 6 different human pluripotent stem cell (hPSC) lines, including a WT1-2A-eGFP knock-in reporter line, under chemically-defined, xeno-free conditions. We also show that treatment with transforming growth factor beta (TGF-β)-signalling inhibitors permitted long-term expansion of the hPSC-derived epicardial cells, resulting in a more than 25 population doublings of WT1+ cells in homogenous monolayers. The hPSC-derived epicardial cells were similar to primary epicardial cells both in vitro and in vivo, as determined by morphological and functional assays, including RNA-seq. Our findings have implications for the understanding of self-renewal mechanisms of the epicardium and for epicardial regeneration using cellular or small-molecule therapies. |
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Geographical breakdown
Country | Count | As % |
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United States | 5 | 18% |
United Kingdom | 2 | 7% |
Italy | 1 | 4% |
Australia | 1 | 4% |
Singapore | 1 | 4% |
Colombia | 1 | 4% |
Greece | 1 | 4% |
Unknown | 16 | 57% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 15 | 54% |
Scientists | 10 | 36% |
Science communicators (journalists, bloggers, editors) | 2 | 7% |
Practitioners (doctors, other healthcare professionals) | 1 | 4% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 146 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 38 | 26% |
Researcher | 22 | 15% |
Student > Master | 15 | 10% |
Student > Bachelor | 14 | 10% |
Professor > Associate Professor | 7 | 5% |
Other | 23 | 16% |
Unknown | 27 | 18% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 30 | 21% |
Agricultural and Biological Sciences | 24 | 16% |
Engineering | 23 | 16% |
Medicine and Dentistry | 14 | 10% |
Chemical Engineering | 5 | 3% |
Other | 17 | 12% |
Unknown | 33 | 23% |