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

Kenichiro Taniguchi; Yue Shao; Ryan F. Townshend; Yu-Hwai Tsai; Cynthia J. DeLong; Shawn A. Lopez; Srimonta Gayen; Andrew M. Freddo; Deming J. Chue; Dennis J. Thomas; Jason R. Spence; Benjamin Margolis; Sundeep Kalantry; Jianping Fu; K. Sue O’Shea; Deborah L. Gumucio

doi:10.1016/j.stemcr.2015.10.015

Stem Cell Reports (Dec 2015)

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

Kenichiro Taniguchi,
Yue Shao,
Ryan F. Townshend,
Yu-Hwai Tsai,
Cynthia J. DeLong,
Shawn A. Lopez,
Srimonta Gayen,
Andrew M. Freddo,
Deming J. Chue,
Dennis J. Thomas,
Jason R. Spence,
Benjamin Margolis,
Sundeep Kalantry,
Jianping Fu,
K. Sue O’Shea,
Deborah L. Gumucio

Affiliations

Kenichiro Taniguchi: Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
Yue Shao: Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI 48109, USA
Ryan F. Townshend: Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
Yu-Hwai Tsai: Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
Cynthia J. DeLong: Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
Shawn A. Lopez: Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
Srimonta Gayen: Department of Human Genetics, University of Michigan Medical School, Ann Arbor, MI 48109, USA
Andrew M. Freddo: Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
Deming J. Chue: Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
Dennis J. Thomas: Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
Jason R. Spence: Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
Benjamin Margolis: Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA
Sundeep Kalantry: Department of Human Genetics, University of Michigan Medical School, Ann Arbor, MI 48109, USA
Jianping Fu: Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI 48109, USA
K. Sue O’Shea: Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
Deborah L. Gumucio: Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA

DOI: https://doi.org/10.1016/j.stemcr.2015.10.015
Journal volume & issue: Vol. 5, no. 6
pp. 954 – 962

Abstract

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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 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.

Published in Stem Cell Reports

ISSN: 2213-6711 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Medicine (General); Science: Biology (General)
Website: http://www.cell.com/stem-cell-reports/home

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