title: Immediate expression of Cdh2 is essential for efficient neural differentiation of mouse induced pluripotent stem cells.
abstract: Induced pluripotent stem cells (iPSCs) exhibit reduced efficiency and higher variability in neural differentiation compared to embryonic stem cells (ESCs). In this study, we showed that mouse iPSCs failed to efficiently give rise to neuronal cells using conventional methods previously established for driving mouse ESC differentiation. We reported a novel approach which remarkably increases neural differentiation of mouse iPSCs. This novel approach initiated embryoid body (EB) formation directly from the whole cell clones isolated from the top of feeder cells. Compared to conventional neural induction methods such as single cell suspension or monolayer culture, the cell clone-derived EB method led to a pronounced increase in directed generation of various types of neural cells including neural stem cells, motoneurons and dopaminergic neurons in response to different inducers. Through gene expression microarray analysis, we identified 14 genes that were highly expressed in the cell clone-derived EBs. Among them, we found that Cdh2, also known as N-cadherin, played important roles in controlling the neural differentiation efficiency of mouse iPSCs. Forced expression of Cdh2 in iPSCs substantially enhanced the differentiation efficiency while knocking-down of Cdh2 by shRNA blocked the neural differentiation. Our results revealed a critical role of Cdh2 in the process of efficient neural differentiation of mouse iPS cells.
authors: Stem Cell and Cancer Biology Group, Chinese Academy of Sciences Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
authors: Huanxing
authors: H
authors: Su
authors: Lihui
authors: L
authors: Wang
authors: Wenhao
authors: W
authors: Huang
authors: Dajiang
authors: D
authors: Qin
authors: Jinglei
authors: J
authors: Cai
authors: Xiaoli
authors: X
authors: Yao
authors: Chengqian
authors: C
authors: Feng
authors: Zhiyuan
authors: Z
authors: Li
authors: Yitao
authors: Y
authors: Wang
authors: Kwok-Fai
authors: KF
authors: So
authors: Guangjin
authors: G
authors: Pan
authors: Wutian
authors: W
authors: Wu
authors: Duanqing
authors: D
authors: Pei
mesh_terms: D000818:Animals; D015820:Cadherins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D002460:Cell Line; D053595:Embryonic Stem Cells / Q000166:cytology; D005786:Gene Expression Regulation; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism* / Q000637:transplantation; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D014184:Transplantation, Homologous
chemical_list: D015820:Cadherins; D034741:RNA, Small Interfering