کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2093698 | 1081974 | 2015 | 9 صفحه PDF | دانلود رایگان |
• Lumen formation is an intrinsic and fundamental property of hESCs
• Two cell clones exhibit highly organized and well-polarized AMIS structures
• Shapes of hESC lumen are malleable when grown in an engineered micro-well system
• Formin- and ARP2/3-dependent actin polymerization promotes lumenogenesis
SummaryWe demonstrate that dissociated human pluripotent stem cells (PSCs) are intrinsically programmed to form lumens. PSCs form two-cell cysts with a shared apical domain within 20 hr of plating; these cysts collapse to form monolayers after 5 days. Expression of pluripotency markers is maintained throughout this time. In two-cell cysts, an apical domain, marked by EZRIN and atypical PKCζ, is surrounded by apically targeted organelles (early endosomes and Golgi). Molecularly, actin polymerization, regulated by ARP2/3 and mammalian diaphanous-related formin 1 (MDIA), promotes lumen formation, whereas actin contraction, mediated by MYOSIN-II, inhibits this process. Finally, we show that lumenal shape can be manipulated in bioengineered micro-wells. Since lumen formation is an indispensable step in early mammalian development, this system can provide a powerful model for investigation of this process in a controlled environment. Overall, our data establish that lumenogenesis is a fundamental cell biological property of human PSCs.
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Journal: - Volume 5, Issue 6, 8 December 2015, Pages 954–962