期刊
STEM CELL RESEARCH & THERAPY
卷 11, 期 1, 页码 -出版社
BMC
DOI: 10.1186/s13287-020-01729-0
关键词
CD133; Human embryonic stem cell; Teratoma
资金
- China National Key RD Program [2018YFA0107000]
- China MOST Program of International ST Cooperation [2014DFA30450]
BackgroundPluripotent stem cells (PSCs), including human embryonic stem cells (hESCs), hold great potential for regenerative medicine and cell therapy. One of the major hurdles hindering the clinical development of PSC-based therapy is the potential risk of tumorigenesis. CD133 (Prominin 1, PROM1) is a transmembrane protein whose mRNA and glycosylated forms are highly expressed in many human cancer cell types. CD133 also serves as a cancer stem cell (CSC) marker associated with cancer progression and patient outcome. Interestingly, CD133 is highly expressed in hESCs as well as in human preimplantation embryos, but its function in hESCs has remained largely unknown.MethodsCD133 knockout hESC WA26 cell line was generated with CRISPR/Cas9. CD133 knockout and wide type hESC lines were subjected to pluripotency, proliferation, telomere biology, and teratoma tests; the related global changes and underlying mechanisms were further systemically analyzed by RNA-seq.ResultsCD133 deficiency did not affect hESC pluripotency or in vivo differentiation into three germ layers but significantly decreased cell proliferation. RNA-seq revealed that CD133 deficiency dysregulated the p53, PI3K-Akt, AMPK, and Wnt signaling pathways. Alterations in these pathways have been implicated in tumor proliferation and apoptotic escape.ConclusionsOur data imply that CD133 could be an additional target and used as a selective marker to sort and eliminate undifferentiated cells in reducing potential teratoma formation risk of hESCs in regenerative medicine.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据