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Cell-extracellular matrix interactions in the fluidic phase direct the topology and polarity of self-organized epithelial structures

Ouyang, Mingxing and Yu, Jiun-Yann and Chen, Yenyu and Deng, Linhong and Guo, Chin-Lin (2020) Cell-extracellular matrix interactions in the fluidic phase direct the topology and polarity of self-organized epithelial structures. . (Unpublished)

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In vivo, cells are surrounded by extracellular matrix (ECM). To build organs from single cells, it is generally believed that ECM serves as a large-scale scaffold to coordinate cell positioning and differentiation. Nevertheless, how cells utilize cell-ECM interactions to spatiotemporally coordinate their positioning and differentiation to different ECM at the whole-tissue scale is not fully understood. Here, using in vitro assay with engineered MDCK cells co-expressing H2B-mCherry (nucleus) and gp135 (Podocalyxin)-GFP (apical marker), we show that such spatiotemporal coordination for epithelial morphogenesis and polarization can be initiated and determined by cell-soluble ECM interaction in the fluidic phase. The coordination depends on the native topology of ECM components such as sheet-like basement membrane (BM, mimicked by Matrigel in experiments) and linear fiber-like type I collagen (COL). Two types of coordination are found: scaffold formed by BM (COL) facilitates a close-ended (open-ended) coordination that leads to the formation of lobular (tubular) epithelium, where polarity is preserved throughout the entire lobule/tubule. During lobular formation with BM, polarization of individual cells within the same cluster occurs almost simultaneously, whereas the apicobasal polarization in the presence of COL can start at local regions and proceed in a collective way along the axis of tubule, which might suggest existence of intercellular communications at the cell-population level. Further, in the fluidic phase, we found that cells can form apicobasal polarity throughout the entire lobule/tubule without a complete coverage of ECM at the basal side. Based on reconstructions from time-lapse confocal imaging, this is likely derived from polarization occurring at early stage and being maintained through growth of the epithelial structures. Under suspension culture with COL, the polarization was impaired with formation of multi-lumens on the tubes, implying the importance of ECM microenvironment for tubulogenesis. Our results suggest a mechanism for cells to form polarity and coordinate positioning in vivo, and a strategy for engineering epithelial structures through cell-soluble ECM interaction and self-assembly in vitro.

Item Type:Report or Paper (Discussion Paper)
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URLURL TypeDescription Paper
Ouyang, Mingxing0000-0001-7265-1695
Deng, Linhong0000-0003-1970-8239
Alternate Title:Extracellular matrix directs the topology and polarity of epithelium
Additional Information:The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. Posted May 14, 2020. We want to thank Dr. Joachim Füllekrug (Max Planck Institute of Molecular Cell Biology and Genetics) for pcDNA3-gp135-GFP construct, and Dr. Rusty Lansford and David Huss (Biology, California Institute of Technology) for Lentivirus encoding H2B-mCherry. This work is financially supported by Ellison Medical Foundation and Western Heaven Funds (C.G.); National Natural Science Foundation of China (NSFC11872129) and Natural Science Foundation of Jiangsu Province (BK20181416) (M.O.); National Natural Science Foundation of China (NSFC11532003) (L.D.). Author Contributions: M. Ouyang and C. Guo designed the research and performed data analysis; M. Ouyang, J-Y Yu, C. Guo conducted the experiments; J-Y Yu, Y Chen, and C. Guo constructed the microscopes and developed the imaging programs; L Deng provided discussion and certain fund support; M. Ouyang, C. Guo and L. Deng prepared the manuscript. the authors declare no conflict of interest in this work.
Funding AgencyGrant Number
Ellison Medical FoundationUNSPECIFIED
Western Heaven FundsUNSPECIFIED
National Natural Science Foundation of ChinaNSFC11872129
Natural Science Foundation of Jiangsu ProvinceBK20181416
National Natural Science Foundation of ChinaNSFC11532003
Subject Keywords:epithelial self-assembly; tubulogenesis; type I collagen; fluidic phase; cell-ECM interaction; epithelial polarity
Record Number:CaltechAUTHORS:20200515-090423680
Persistent URL:
Official Citation:Cell-extracellular matrix interactions in the fluidic phase direct the topology and polarity of self-organized epithelial structures. Mingxing Ouyang, Jiun-Yann Yu, Yenyu Chen, Linhong Deng, Chin-Lin Guo. bioRxiv 2020.05.12.090068; doi:
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:103227
Deposited By: Tony Diaz
Deposited On:15 May 2020 16:14
Last Modified:23 Jun 2020 22:03

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