title: Lumen Formation Is an Intrinsic Property of Isolated Human Pluripotent Stem Cells.
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.
authors.affiliation: Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA. Electronic address: taniguch@med.umich.edu.
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Taniguchi
authors.affiliation: Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Yue
authors.initials: Y
authors.lastname: Shao
authors.affiliation: Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Ryan F
authors.initials: RF
authors.lastname: Townshend
authors.affiliation: 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.
authors.forename: Yu-Hwai
authors.initials: YH
authors.lastname: Tsai
authors.affiliation: Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Cynthia J
authors.initials: CJ
authors.lastname: DeLong
authors.affiliation: Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Shawn A
authors.initials: SA
authors.lastname: Lopez
authors.affiliation: Department of Human Genetics, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Srimonta
authors.initials: S
authors.lastname: Gayen
authors.affiliation: Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Freddo
authors.affiliation: Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Deming J
authors.initials: DJ
authors.lastname: Chue
authors.affiliation: Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Dennis J
authors.initials: DJ
authors.lastname: Thomas
authors.affiliation: 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.
authors.forename: Jason R
authors.initials: JR
authors.lastname: Spence
authors.affiliation: 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.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Margolis
authors.affiliation: Department of Human Genetics, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Sundeep
authors.initials: S
authors.lastname: Kalantry
authors.affiliation: Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Jianping
authors.initials: J
authors.lastname: Fu
authors.affiliation: Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: K Sue
authors.initials: KS
authors.lastname: O'Shea
authors.affiliation: Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA. Electronic address: dgumucio@med.umich.edu.
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Gumucio
mesh_terms: D000199:Actins / Q000378:metabolism / Q000648:ultrastructure; D000818:Animals; D018929:Cell Culture Techniques; D002460:Cell Line; D002469:Cell Separation; D048430:Cell Shape; D004285:Dogs; D006801:Humans; D051379:Mice; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D000199:Actins