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Biochim Biophys Acta Mol Cell Res. 2019 Jun;1866(6):971-977. doi: 10.1016/j.bbamcr.2019.03.001. Epub 2019 Mar 9.

Long-term self-renewal of naïve neural stem cells in a defined condition.

Author information

1
Department of Neurology, Nan-Fang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China. Electronic address: yongmingwucn@hotmail.com.
2
Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, Department of Stem Cell Biology & Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, United States of America.
3
Department of Neurology, Wuxi People's Hospital of Nanjing Medical University, Wuxi, Jiangsu 214023, China.
4
Department of Neurology, Nan-Fang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
5
Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, Department of Stem Cell Biology & Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, United States of America. Electronic address: qying@med.usc.edu.

Abstract

During embryonic development, neural stem cells (NSCs) emerge as early as the neural plate stage and give rise to the nervous system. Early-stage NSCs express Sry-related-HMG box-1 (Sox1) and are biased towards neuronal differentiation. However, long-term maintenance of early-stage NSCs in vitro remains a challenge. Here, we report development of a defined culture condition for the long-term maintenance of Sox1-positive early-stage mouse NSCs. The proliferative ability of these Sox1-positive NSCs was confirmed by clonal propagation. Compared to the NSCs cultured using the traditional culture condition, the long-term self-renewing Sox1-positive NSCs efficiently differentiate into neurons and exhibit an identity representative of the anterior and midbrain regions. These early-stage Sox1-positive NSCs could also be switched to late-stage NSCs by being cultured with bFGF/EGF, which can then differentiate into astrocytes and oligodendrocytes. The long-term self-renewing Sox1-positive NSCs were defined as naïve NSCs, based on their high neuronal differentiation capacity and anterior regional identity. This culture condition provides a robust platform for further dissection of the NSC self-renewal mechanism and promotes potential applications of NSCs for cell-based therapy on nervous system disorders.

KEYWORDS:

Cell culture; Cell signaling; Cytokines; Neural stem cells (NSCs); Self-renewal

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