Rapid induction and long-term self-renewal of primitive neural precursors from human embryonic stem cells by small molecule inhibitors
- Authors
- Li, Wenlin; Sun, Woong; Zhang, Yu; Wei, Wanguo; Ambasudhan, Rajesh; Xia, Peng; Talantova, Maria; Lin, Tongxiang; Kim, Janghwan; Wang, Xiaolei; Kim, Woon Ryoung; Lipton, Stuart A.; Zhang, Kang; Ding, Sheng
- Issue Date
- 17-5월-2011
- Publisher
- NATL ACAD SCIENCES
- Citation
- PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v.108, no.20, pp.8299 - 8304
- Indexed
- SCIE
SCOPUS
- Journal Title
- PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
- Volume
- 108
- Number
- 20
- Start Page
- 8299
- End Page
- 8304
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/112444
- DOI
- 10.1073/pnas.1014041108
- ISSN
- 0027-8424
- Abstract
- Human embryonic stem cells (hESCs) hold enormous promise for regenerative medicine. Typically, hESC-based applications would require their in vitro differentiation into a desirable homogenous cell population. A major challenge of the current hESC differentiation paradigm is the inability to effectively capture and, in the long-term, stably expand primitive lineage-specific stem/precursor cells that retain broad differentiation potential and, more importantly, developmental stage-specific differentiation propensity. Here, we report synergistic inhibition of glycogen synthase kinase 3 (GSK3), transforming growth factor beta (TGF-beta), and Notch signaling pathways by small molecules can efficiently convert monolayer cultured hESCs into homogenous primitive neuroepithelium within 1 wk under chemically defined condition. These primitive neuroepithelia can stably self-renew in the presence of leukemia inhibitory factor, GSK3 inhibitor (CHIR99021), and TGF-beta receptor inhibitor (SB431542); retain high neurogenic potential and responsiveness to instructive neural patterning cues toward midbrain and hindbrain neuronal subtypes; and exhibit in vivo integration. Our work uniformly captures and maintains primitive neural stem cells from hESCs.
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Collections - Graduate School > Department of Biomedical Sciences > 1. Journal Articles
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