Rapid induction and long-term self-renewal of primitive neural precursors from human embryonic stem cells by small molecule inhibitors
Year: 2011
Type: article
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 β (TGF-β), 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-β 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.
Institutions: Scripps Research Institute, Second Military Medical University, Korea University, Korea University Medical Center, University of California San Diego, Sanford Burnham Prebys Medical Discovery Institute, Sichuan University, West China Hospital of Sichuan University, University of California, San Francisco
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Funders: Prostate Cancer Foundation, California Institute for Regenerative Medicine, Research to Prevent Blindness, Macula Vision Research Foundation, Sichuan University, National Institutes of Health, West China Hospital, Sichuan University, National Heart, Lung, and Blood Institute, National Institute of Mental Health, National Eye Institute, National Institute of Neurological Disorders and Stroke, National Institute of Environmental Health Sciences
OpenAlex ID: W2168250872