Journal
STEM CELL REPORTS
Volume 5, Issue 6, Pages 954-962Publisher
CELL PRESS
DOI: 10.1016/j.stemcr.2015.10.015
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Funding
- NIH [R01-DK089933, T32-HD007505, F30-DK100125, R01-DK69605, DP2-OD-008646-01, R21-EB017078, R21-HL114011, K01-DK091415]
- March of Dimes
- National Science Foundation [CBET1149401]
- Schwartzberg Memorial Fund
- Prechter Fund
- Div Of Chem, Bioeng, Env, & Transp Sys
- Directorate For Engineering [1149401] Funding Source: National Science Foundation
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We 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 PKCz, 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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