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STAMBP is Required for Long-Term Maintenance of Neural Progenitor Cells Derived from hESCs.
Zhang, Jitian; Zhang, Yanqi; Liu, Yancai; Zhou, Tiancheng; Pan, Guangjin; He, Jufang; Shu, Xiaodong.
Afiliação
  • Zhang J; Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China.
  • Zhang Y; Department of Neuroscience, City University of Hong Kong, Hong Kong, China.
  • Liu Y; Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China.
  • Zhou T; Divison of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230027, China.
  • Pan G; Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China.
  • He J; Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China.
  • Shu X; Department of Neuroscience, City University of Hong Kong, Hong Kong, China. jufanghe@cityu.edu.hk.
Stem Cell Rev Rep ; 20(7): 1932-1943, 2024 Oct.
Article em En | MEDLINE | ID: mdl-38951308
ABSTRACT
Mutations in STAMBP have been well-established to cause congenital human microcephaly-capillary malformation (MIC-CAP) syndrome, a rare genetic disorder characterized by global developmental delay, severe microcephaly, capillary malformations, etc. Previous biochemical investigations and loss-of-function studies in mice have provided insights into the mechanism of STAMBP, however, it remains controversial how STAMBP deficiency leads to malformation of those affected tissues in patients. In this study, we investigated the function and underlying mechanism of STAMBP during neural differentiation of human embryonic stem cells (hESCs). We found that STAMBP is dispensable for the pluripotency maintenance or neural differentiation of hESCs. However, neural progenitor cells (NPCs) derived from STAMBP-deficient hESCs fail to be long-term maintained/expanded in vitro. We identified the anti-apoptotic protein CFLAR is down-regulated in those affected NPCs and ectopic expression of CFLAR rescues NPC defects induced by STAMBP-deficiency. Our study not only provides novel insight into the mechanism of neural defects in STAMBP mutant patients, it also indicates that the death receptor mediated apoptosis is an obstacle for long-term maintenance/expansion of NPCs in vitro thus counteracting this cell death pathway could be beneficial to the generation of NPCs in vitro.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Diferenciação Celular / Células-Tronco Neurais / Células-Tronco Embrionárias Humanas Limite: Animals / Humans Idioma: En Revista: Stem Cell Rev Rep Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Diferenciação Celular / Células-Tronco Neurais / Células-Tronco Embrionárias Humanas Limite: Animals / Humans Idioma: En Revista: Stem Cell Rev Rep Ano de publicação: 2024 Tipo de documento: Article