Pluripotent stem cells (including embryonic stem cells and induced pluripotent stem cells) are characterized by their unlimited self-renewability in culture and generative capability to give rise to all cells, tissues, and organs in our body, which provide us with a powerful tool for developing novel insights into basic biology and new translational applications. Our research group mainly focuses on the basic and translational studies using pluripotent stem cells from different species (including humans, mice, rats, monkeys, pigs, horses, cows, ground squirrels etc.), different pluripotent states (naive, formative, and primed), and both embryonic and extra-embryonic lineages. Combined with microfluidics and other engineering technologies to simulate the microenvironment of early embryonic development, to reproduce key events during early embryonic development in vitro, thus studying the early embryonic development and its related diseases.

Generation of human blastoids (Yu et al. 2021 Nature)

Generation of formative pluripotent stem cells (Yu et al. 2021 Cell Stem Cell)

Our main research focuses include:
1. Development of pluripotent stem cell-based models modeling early development, organogenesis, and diseases.
2. Studying the key events of early human early development by utilizing the micro-engineering tools
3. Generations and applications of novel stable pluripotent stem cells from different species.

Selected publications:

1. Yu, L. #; Wei, Y. #; Duan, J. #; Schmitz, D. A.; Sakurai, M.; Wang, L.; Wang, K.; Zhao, S.; Hon, G. C.*; Wu, J.*, Blastocyst-like structures generated from human pluripotent stem cells, Nature, 2021 (# Co-frist authors)

• Selected as 2021 Breakthrough of the Year 2021 by Science, Vol 374, Issue 6574
• Selected as the front cover page story by Nature, Vol. 591, Issue 7851
• Commentary by Jianping Fu, “First complete model of the human embryo” Nature, DOI: 10.1038/d41586-021-00581-3
• Nature News by Nidhi Subbaraman, “Lab-grown structures mimic human embryo's earliest stage yet”
• Also highlighted by Science News, US News, New York Times, NHK News, Asahi News, NBC News, Dayton Daily News, Nobel Intent, etc.

2. Liu, T. #; Li, J. #; Yu, L. #; Sun, H.; Li, J.; Dong, G.; Hu, Y.; Li, Y.; Shen, Y.; Wu, J.*; Gu, Y.*, Cross-species single-cell transcriptomic analysis reveals pre-gastrulation developmental differences among pigs, monkeys, and humans, Cell discovery, 2021 (# Co-frist authors)
3. Zheng, C. #; Hu, Y. #; Sakurai, M. #; Pinzon-Arteaga, C. A.; Li, J.; Wei, Y.; Okamura, D.; Ravaux, B.; Barlow, H. R.; Yu, L.; Sun, H.; Chen, E. H.; Gu, Y.; Wu, J.*, Cell competition constitutes a barrier for interspecies chimerism, Nature, 2021
4. Yu, L.#; Logsdon, D. #; Pinzon-Arteaga, C.A. #; Duan, J. #; Ezashi, T. #; Wei, Y. #; Oura, S.; Liu, L.; Wang, L.; Liu, K.; Ding, X.; Zhan, L.; Zhang, J.; Nahar, A.; Stobbe, C.; Katz-Jaffe, M.; Schoolcraft, W.B.; Tan, T.; Hon, G.C. *; Yuan, Y. *; Wu, J.*, Large-scale production of human blastoids amenable to modeling blastocyst development and maternal-fetal cross talk, Cell Stem Cell, 2023 (# Co-frist authors)
5. Wu, X.#; Zhao, W.;#, Wu, H.#; Zhang, Q.#; Wang, Y.; Yu, K.; Zhai, J.; Mo, F.; Wang, M.; Li, S.; Zhu, X.; Liang, X.; Hu, B.; Liu, G. H.; Wu, J. *; Wang, H. *; Guo, F. *; Yu, L.*, An aggregation of human embryonic and trophoblast stem cells reveals the role of trophectoderm on epiblast differentiation, Cell proliferation, 2023(# Co-frist authors)
6. Wei Y#, Zhang E#, Yu L#, Ci B#, Sakurai M, Guo L, Zhang X, Lin S, Takii S, Liu L, Liu J, Schmitz DA, Su T, Zhang J, Shen Q, Ding Y, Zhan L, Sun HX, Zheng C, Xu L, Okamura D, Ji W*, Tan T*, Wu J*. Dissecting embryonic and extraembryonic lineage crosstalk with stem cell co-culture.,Cell.,2023(# Co-frist authors)
7. Yu, L. #; Wei, Y. #; Sun, H. #; Mahdi, A. K.; Pinzon Arteaga, C. A.; Sakurai, M.; Schmitz, D. A.; Zheng, C.; Ballard, E. D.; Li, J.; Tanaka, N.; Kohara, A.; Okamura, D.; Mutto, A. A.; Gu, Y.; Ross, P. J.; Wu, J.*, Derivation of Intermediate Pluripotent Stem Cells Amenable to Primordial Germ Cell Specification, Cell Stem Cell, 2020 (# Co-frist authors)

• Commentary by Ng Shyh-Chang & Lei Li, “Stabilizing Formative Pluripotent States with Germ Cell Competency” Cell Stem Cell, DOI: 10.1016/j.stem.2021.02.021
• Commentary by Stefan H. A. Hoogland & Hendrik Marks, “Developments in pluripotency: a new formative state” Cell Research, DOI: 10.1038/s41422-021-00494-w
• Highlighted by ScienceDaily News, “Development of new stem cell type may lead to advances in regenerative medicine”
• Highlighted by GEN News, “New Stem Cell Derived from Mice, Horses, and Humans”

8. Vilarino, M.; Soto, D.A.; Bogliotti, Y. S.; Yu, L.; Zhang, Y.; Wang, C.; Paulson, E.; Zhong, C.; Jin, C.; Izpisua Belmonte, J. C.; Wu, J.; Ross, P .J.*, Derivation of sheep embryonic stem cells under optimized conditions. Reproduction, 2020
9. Li, J. #; Zhang, L. #; Yu, L.; Minami, I.; Miyagawa, S.; Horning, M.; Dong, J.; Qiao, J.; Qu, X.; Hua, Y.; Fujimoto, N.; Shiba, Y.; Zhao, Y.; Tang, F.; Chen, Y.; Sawa, Y.*; Tang, C.*; Liu, L.*, Circulating re-entrant waves promote maturation of hiPSC-derived cardiomyocytes in self-organized tissue ring, Communications biology, 2020
10. Yu, L. #; Li, J. #; Itsunari, M.; Qu, X.; Miyagawa, S.; Fujimoto, N.; Hasegawa, K.; Chen, Y.; Sawa, Y.; Kotera, H.; Liu, L.*, Clonal Isolation of Human Pluripotent Stem Cells on Nanofibrous Substrates Reveals an Advanced Subclone for Cardiomyocyte Differentiation. Advanced Healthcare Materials, 2019 (# Co-frist authors)

• Selected as the cover page story by Advanced Healthcare Materials

11. Li, R. #; Zhong, C. #; Yu, Y. #; Liu, H.; Sakurai, M.; Yu, L.; Min, Z.; Shi, L.; Wei, Y.; Takahashi, Y.; Liao, H.; Qiao, J.; Deng, H.; Nunez-Delicado, E.; Rodriguez Esteban, C.; Wu, J. *; Izpisua Belmonte, J. C.*; Generation of Blastocyst-like Structures from Mouse Embryonic and Adult Cell Cultures. Cell, 2019
12. Zhang, Y.; Li, T.; Preissl, S.; Amaral, M.L.; Grinstein, J.D.; Farah, E.N.; Destici, E.; Qiu, Y.; Hu, R. Lee, A.Y.; Chee, S.; Ma, K.; Ye, Z.; Zhu, Q.; Huang, H.; Fang, R.; Yu, L.; Izpisua Belmonte, J.C.; Wu, J.; Evans, S.M.; Chi, N.C.*; Ren B*. Transcriptionally active HERV-H retrotransposons demarcate topologically associating domains in human pluripotent stem cells. Nature Genetics, 2019
13. Xu, J.; Yu, L.; Guo, J.; Xiang, J.; Zheng, Z.; Gao, D.; Shi, B.; Hao, H.; Jiao, D.; Zhong, L.; Wang, Y.; Wu, J.*; Wei, H. *; Han, J*. Generation of pig induced pluripotent stem cells using an extended pluripotent stem cell culture system. Stem Cell Research & Therapy, 2019
14. Yu, L.; Li, J.; Hong, J.; Takashima, Y.; Fujimoto, N.; Nakajima, M.; Dong, X.; Dang, Y.; Yang, W.; Okita, K.; Luo, C.; Tang, F.; Chen, Y.; Tang, C.*; Kotera, H.*; Liu, L.*, Low Cell-Matrix Adhesion Reveals Two Novel Subtypes of Human Pluripotent Stem Cells. Stem Cell Reports, 2018
15. Li, J. #; Minami, I. #; Yu, L.; Shiozaki, M.; Shiba, Y.; Yajima, S.; Morone, N.; Fukushima, S.; Yoshioka, M.; Li, S.; Qiao, J.; Li, X.; Wang, L.; Kotera, H.; Miyagawa, S.; Nakatsuji, N.; Sawa, Y.; Chen, Y.; Liu, L., Human Pluripotent Stem Cell-Derived Cardiac Tissue-Like Constructs for Repairing of the Infarcted Myocardium. Stem Cell Reports, 2017
16. Li, J.; Zhang, F.; Yu, L.; Fujimoto, N.; Yoshioka, M.; Li, X.; Shi, J.; Kotera, H.; Liu, L.* and Chen, Y. * , Culture substrates made of elastomeric micro-tripod arrays for long-term expansion of human pluripotent stem cells, J. Mater. Chem. B, 2017
17. Li, X.#; Yu, L.#; Li, J.; Minami, I.; Nakajima, M.; Noda, Y.; Kotera, H.; Liu, L.*; Chen, Y.*, On chip purification of hiPSC-derived cardiomyocytes using a fishnet-like microstructure, Biofabrication, 2016. (# Co-frist authors)
18. Tang, Y.; Liu, L.; Li, J.; Yu, L.; Wang, L.; Shi, J.; Chen, Y.*, Induction and Differentiation of Human Induced Pluripotent Stem Cells into Functional Cardiomyocytes on a Compartmented Monolayer of Gelatin Nanofibers. Nanoscale, 2016
19. Li, J.; Minami, I.; Yu, L.; Tsuji, K.; Nakajima, M.; Qiao, J.; Suzuki, M.; Shimono, K.; Nakatsuji, N.; Kotera, H.; Liu, L.*; Chen, Y.*, Extracellular Recordings of Patterned Human Pluripotent Stem Cell-Derived Cardiomyocytes on Aligned Fibers. Stem cells international, 2016
20. Tang, Y.; Liu, L.; Li, J.; Yu, L.; Severino, F. P. U.; Wang, L.; Shi, J.; Tu, X.; Torre, V.; Chen, Y.*, Effective Motor Neuron Differentiation of Hipscs on a Patch Made of Crosslinked Monolayer Gelatin Nanofibers. Journal of Materials Chemistry B, 2016