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

被引：90

作者：

Taniguchi, Kenichiro ^{[1
]}

Shao, Yue

Townshend, Ryan F. ^{[1
]}

Tsai, Yu-Hwai ^{[1
,2
]}

DeLong, Cynthia J. ^{[1
]}

Lopez, Shawn A. ^{[1
]}

Gayen, Srimonta ^{[3
]}

Freddo, Andrew M. ^{[1
]}

Chue, Deming J. ^{[1
]}

Thomas, Dennis J. ^{[1
]}

Spence, Jason R. ^{[1
,2
]}

Margolis, Benjamin ^{[2
,4
]}

Kalantry, Sundeep ^{[3
]}

Fu, Jianping ^{[5
]}

O'Shea, K. Sue ^{[1
]}

Gumucio, Deborah L. ^{[1
]}

机构：

[1] Univ Michigan, Sch Med, Dept Cell & Dev Biol, Ann Arbor, MI 48109 USA

[2] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI 48109 USA

[3] Univ Michigan, Sch Med, Dept Human Genet, Ann Arbor, MI 48109 USA

[4] Univ Michigan, Sch Med, Dept Biol Chem, Ann Arbor, MI 48109 USA

[5] Univ Michigan, Dept Mech Engn, Ann Arbor, MI 48109 USA

来源：

STEM CELL REPORTS | 2015年 / 5卷 / 06期

基金：

美国国家科学基金会;

关键词：

STATE; CYTOKINESIS; POLARITY;

D O I：

10.1016/j.stemcr.2015.10.015

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

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.

引用

页码：954 / 962

页数：9

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