Journal
JOURNAL OF CELL BIOLOGY
Volume 216, Issue 12, Pages 3981-3990Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.201704085
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Funding
- National Institutes of Health [R01-DK089933, T32-HD007505, R21-EB017078, R21-HL114011, DP2-OD-008646]
- National Science Foundation [CBET1149401]
- March of Dimes Basil O'Connor Starter Scholar Research Award [5-FY12-119]
- University of Michigan Rackham Predoctoral Fellowship
- University of Michigan Phi-Kappa-Phi Honor Society Student Grant
- Steven Schwartzberg Memorial Fund
- Prechter Fund
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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.
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