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J Cell Biol. 2017 Dec 4;216(12):3981-3990. doi: 10.1083/jcb.201704085. Epub 2017 Oct 11.

An apicosome initiates self-organizing morphogenesis of human pluripotent stem cells.

Author information

1
Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI taniguch@med.umich.edu.
2
Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI.
3
Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI.
4
Department of Human Genetics, University of Michigan Medical School, Ann Arbor, MI.
5
Microscopy and Image Analysis Laboratory, University of Michigan Medical School, Ann Arbor, MI.
6
Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI.
7
Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI dgumucio@med.umich.edu.

Abstract

Human pluripotent stem cells (hPSCs) self-organize into apicobasally polarized cysts, reminiscent of the lumenal epiblast stage, providing a model to explore key morphogenic processes in early human embryos. Here, we show that apical polarization begins on the interior of single hPSCs through the dynamic formation of a highly organized perinuclear apicosome structure. The membrane surrounding the apicosome is enriched in apical markers and displays microvilli and a primary cilium; its lumenal space is rich in Ca2+ Time-lapse imaging of isolated hPSCs reveals that the apicosome forms de novo in interphase, retains its structure during mitosis, is asymmetrically inherited after mitosis, and relocates to the recently formed cytokinetic plane, where it establishes a fully polarized lumen. In a multicellular aggregate of hPSCs, intracellular apicosomes from multiple cells are trafficked to generate a common lumenal cavity. Thus, the apicosome is a unique preassembled apical structure that can be rapidly used in single or clustered hPSCs to initiate self-organized apical polarization and lumenogenesis.

PMID:
29021220
PMCID:
PMC5716285
DOI:
10.1083/jcb.201704085
[Indexed for MEDLINE]
Free PMC Article

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