Multivariate patterning of human pluripotent cells under perfusion reveals critical roles of induced paracrine factors in kidney organoid development.

Autor:	Glass NR; Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St. Lucia, QLD 4072, Australia., Takasako M; Institute for Molecular Bioscience, The University of Queensland, St. Lucia 4072, Australia.; Murdoch Children's Research Institute, Flemington Rd., Parkville, VIC 3052, Australia., Er PX; Institute for Molecular Bioscience, The University of Queensland, St. Lucia 4072, Australia.; Murdoch Children's Research Institute, Flemington Rd., Parkville, VIC 3052, Australia., Titmarsh DM; Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St. Lucia, QLD 4072, Australia., Hidalgo A; Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St. Lucia, QLD 4072, Australia., Wolvetang EJ; Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St. Lucia, QLD 4072, Australia.; UQ Centre in Stem Cell and Regenerative Engineering, The University of Queensland, St. Lucia, QLD 4072, Australia., Little MH; Institute for Molecular Bioscience, The University of Queensland, St. Lucia 4072, Australia.; Murdoch Children's Research Institute, Flemington Rd., Parkville, VIC 3052, Australia.; Department of Pediatrics, University of Melbourne, Parkville, VIC 3052, Australia., Cooper-White JJ; Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St. Lucia, QLD 4072, Australia.; UQ Centre in Stem Cell and Regenerative Engineering, The University of Queensland, St. Lucia, QLD 4072, Australia.; Biomedical Manufacturing, Manufacturing Flagship, CSIRO, Clayton, VIC 3169, Australia.; School of Chemical Engineering, The University of Queensland, St. Lucia, QLD 4072, Australia.
Jazyk:	angličtina
Zdroj:	Science advances [Sci Adv] 2020 Jan 08; Vol. 6 (2), pp. eaaw2746. Date of Electronic Publication: 2020 Jan 08 (Print Publication: 2020).
DOI:	10.1126/sciadv.aaw2746
Abstrakt:	Creating complex multicellular kidney organoids from pluripotent stem cells shows great promise. Further improvements in differentiation outcomes, patterning, and maturation of specific cell types are, however, intrinsically limited by standard tissue culture approaches. We describe a novel full factorial microbioreactor array-based methodology to achieve rapid interrogation and optimization of this complex multicellular differentiation process in a facile manner. We successfully recapitulate early kidney tissue patterning events, exploring more than 1000 unique conditions in an unbiased and quantitative manner, and define new media combinations that achieve near-pure renal cell type specification. Single-cell resolution identification of distinct renal cell types within multilayered kidney organoids, coupled with multivariate analysis, defined the definitive roles of Wnt, fibroblast growth factor, and bone morphogenetic protein signaling in their specification, exposed retinoic acid as a minimal effector of nephron patterning, and highlighted critical contributions of induced paracrine factors on cell specification and patterning. (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)
Databáze:	MEDLINE
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