Predictive microfluidic control of regulatory ligand trajectories in individual pluripotent cells.

Proceedings of the National Academy of Sciences of the United States of America
Faisal MoledinaPeter W Zandstra

Abstract

Local (cell-level) signaling environments, regulated by autocrine and paracrine signaling, and modulated by cell organization, are hypothesized to be fundamental stem cell fate control mechanisms used during development. It has, however, been challenging to demonstrate the impact of cell-level organization on stem cell fate control and to relate stem cell fate outcomes to autocrine and paracrine signaling. We address this fundamental problem using a combined in silico and experimental approach in which we directly manipulate, using laminar fluid flow, the local impact of endogenously secreted gp130-activating ligands and their activation of signal transducer and activator of transcription3 (STAT3) signaling in mouse embryonic stem cells (mESC). Our model analysis predicted that flow-dependent changes in autocrine and paracrine ligand binding would impact heterogeneity in cell- and colony-level STAT3 signaling activation and cause a gradient of cell fate determination along the direction of flow. Interestingly, analysis also predicted that local cell density would be inversely proportional to the degree to which endogenous secretion contributed to cell fate determination. Experimental validation using functional activation of ST...Continue Reading

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Citations

Nov 13, 2012·Analytical Chemistry·Michelle L KovarikNancy L Allbritton
Nov 22, 2012·Stem Cell Research & Therapy·Krista M FridleyTodd C McDevitt
Mar 22, 2013·PLoS Computational Biology·Douglas E WhiteMelissa L Kemp
Jun 30, 2014·Nature Methods·Aryeh WarmflashAli H Brivanlou
Jan 17, 2014·Tissue Engineering. Part a·Jeanne F LoringRobert M Nerem
Mar 14, 2013·BioNanoScience·Cheston Hsiao, Sean P Palecek
Dec 12, 2012·Trends in Biotechnology·Melissa A Kinney, Todd C McDevitt
Apr 25, 2012·Current Opinion in Chemical Biology·Véronique LecaultCarl L Hansen
Mar 27, 2012·Current Opinion in Biotechnology·Curtis Woodford, Peter W Zandstra
Aug 28, 2015·Current Opinion in Genetics & Development·Tongcheng QianSean P Palecek
Jul 3, 2013·Biotechnology Journal·Drew M TitmarshJustin J Cooper-White
Nov 14, 2013·Biotechnology and Bioengineering·Ryosuke YoshimitsuToshiyuki Kanamori
Feb 4, 2014·Current Opinion in Biotechnology·Camilla LuniNicola Elvassore
Jun 2, 2015·Nature Methods·Giovanni G GiobbeNicola Elvassore
Apr 19, 2016·Nature Methods·Camilla LuniNicola Elvassore
Apr 19, 2015·Stem Cell Research & Therapy·Joseph D BerryDavid N Haylock
Aug 3, 2013·Biotechnology Advances·Laura OrdovásCatherine M Verfaillie
Jul 13, 2016·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Idse Heemskerk, Aryeh Warmflash
Jul 16, 2013·Journal of Laboratory Automation·Ken-ichiro Kamei
May 29, 2015·Lab on a Chip·Ali Oskooei, Axel Günther
Nov 2, 2013·World Journal of Stem Cells·Meimei LiuShang-Tian Yang
Sep 20, 2012·Integrative Biology : Quantitative Biosciences From Nano to Macro·Kento OnishiPeter W Zandstra
Sep 26, 2013·Lab on a Chip·Stefano GiulittiNicola Elvassore
Jan 31, 2018·Molecular Systems Biology·Ayako Yachie-KinoshitaPeter W Zandstra
Sep 23, 2014·Small·Sofia NahavandiKhashayar Khoshmanesh
Nov 19, 2013·Molecular Endocrinology·Guy A Rutter, David J Hodson
Apr 20, 2013·Lab on a Chip·Steffen CossonMatthias P Lutolf
Feb 9, 2018·Chemical Reviews·Deborah HuberGovind V Kaigala

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