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Stem Cell Reports. 2015 Dec 8;5(6):954-962. doi: 10.1016/j.stemcr.2015.10.015. Epub 2015 Nov 25.

Lumen Formation Is an Intrinsic Property of Isolated Human Pluripotent Stem Cells.

Author information

1
Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA. Electronic address: taniguch@med.umich.edu.
2
Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI 48109, USA.
3
Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
4
Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
5
Department of Human Genetics, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
6
Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
7
Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA. Electronic address: dgumucio@med.umich.edu.

Abstract

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 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.

PMID:
26626176
PMCID:
PMC4682207
DOI:
10.1016/j.stemcr.2015.10.015
[Indexed for MEDLINE]
Free PMC Article

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