{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T13:02:46Z","timestamp":1762866166329},"reference-count":64,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2013,3,14]],"date-time":"2013-03-14T00:00:00Z","timestamp":1363219200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"DOI":"10.1371\/journal.pcbi.1002952","type":"journal-article","created":{"date-parts":[[2013,3,14]],"date-time":"2013-03-14T23:39:01Z","timestamp":1363304341000},"page":"e1002952","update-policy":"http:\/\/dx.doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":33,"title":["Spatial Pattern Dynamics of 3D Stem Cell Loss of Pluripotency via Rules-Based Computational Modeling"],"prefix":"10.1371","volume":"9","author":[{"given":"Douglas E.","family":"White","sequence":"first","affiliation":[]},{"given":"Melissa A.","family":"Kinney","sequence":"additional","affiliation":[]},{"given":"Todd C.","family":"McDevitt","sequence":"additional","affiliation":[]},{"given":"Melissa L.","family":"Kemp","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2013,3,14]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1263\/jbb.103.389","article-title":"Methods for inducing embryoid body formation: in vitro differentiation system of embryonic stem cells","volume":"103","author":"H Kurosawa","year":"2007","journal-title":"J Biosci Bioeng"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1002\/btpr.139","article-title":"Engineering the embryoid body microenvironment to direct embryonic stem cell differentiation","volume":"25","author":"AM Bratt-Leal","year":"2009","journal-title":"Biotechnol Prog"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1006\/jmcc.2000.1128","article-title":"Differentiation of cardiomyocytes in floating embryoid bodies is comparable to fetal cardiomyocytes","volume":"32","author":"PA Doevendans","year":"2000","journal-title":"J Mol Cell Cardiol"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1007\/BF03401776","article-title":"Differentiation of human embryonic stem cells into embryoid bodies compromising the three embryonic germ layers","volume":"6","author":"J Itskovitz-Eldor","year":"2000","journal-title":"Mol Med"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1111\/j.1469-445X.2000.02104.x","article-title":"Embryoid bodies: an in vitro model of mouse embryogenesis","volume":"85","author":"I Desbaillets","year":"2000","journal-title":"Exp Physiol"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/S0925-4773(99)00339-1","article-title":"Embryonic stem cell-derived chondrogenic differentiation in vitro: activation by BMP-2 and BMP-4","volume":"92","author":"J Kramer","year":"2000","journal-title":"Mech Dev"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1053\/jhep.2002.34136","article-title":"Embryoid-body cells derived from a mouse embryonic stem cell line show differentiation into functional hepatocytes","volume":"36","author":"R Chinzei","year":"2002","journal-title":"Hepatology"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"3413","DOI":"10.1016\/j.biomaterials.2011.01.036","article-title":"Engineering spatial control of multiple differentiation fates within a stem cell population","volume":"32","author":"ED Ker","year":"2011","journal-title":"Biomaterials"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"3972","DOI":"10.1002\/pmic.201100063","article-title":"Temporal proteomic profiling of embryonic stem cell secretome during cardiac and neural differentiation","volume":"11","author":"A Farina","year":"2011","journal-title":"Proteomics"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1038\/ncb2314","article-title":"Embryonic stem cells require Wnt proteins to prevent differentiation to epiblast stem cells","volume":"13","author":"D ten Berge","year":"2011","journal-title":"Nat Cell Biol"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"19747","DOI":"10.1074\/jbc.M109.077347","article-title":"Nodal signaling regulates the bone morphogenic protein pluripotency pathway in mouse embryonic stem cells","volume":"285","author":"KE Galvin","year":"2010","journal-title":"J Biol Chem"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"1855","DOI":"10.1089\/ten.tea.2008.0227","article-title":"Enhancing osteogenic differentiation of mouse embryonic stem cells by nanofibers","volume":"15","author":"LA Smith","year":"2009","journal-title":"Tissue Eng Part A"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"5094","DOI":"10.1016\/j.biomaterials.2012.04.003","article-title":"Characterization and neural differentiation of mouse embryonic and induced pluripotent stem cells on cadherin-based substrata","volume":"33","author":"A Haque","year":"2012","journal-title":"Biomaterials"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"3005","DOI":"10.1634\/stemcells.2007-0103","article-title":"Integrins regulate mouse embryonic stem cell self-renewal","volume":"25","author":"Y Hayashi","year":"2007","journal-title":"Stem Cells"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"2238","DOI":"10.1098\/rstb.2011.0005","article-title":"Mapping the networks for pluripotency","volume":"366","author":"K Xue","year":"2011","journal-title":"Philos Trans R Soc Lond B Biol Sci"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1042\/BJ20102152","article-title":"Regulation of embryonic stem cell self-renewal and pluripotency by leukaemia inhibitory factor","volume":"438","author":"H Hirai","year":"2011","journal-title":"Biochem J"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1002\/1097-0290(20000920)69:6<607::AID-BIT4>3.0.CO;2-F","article-title":"Leukemia inhibitory factor (LIF) concentration modulates embryonic stem cell self-renewal and differentiation independently of proliferation","volume":"69","author":"PW Zandstra","year":"2000","journal-title":"Biotechnol Bioeng"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/B978-0-12-386015-6.00022-6","article-title":"Factors regulating pluripotency and differentiation in early mammalian embryos and embryo-derived stem cells","volume":"87","author":"A Suwinska","year":"2011","journal-title":"Vitam Horm"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1111\/j.1749-0774.2002.tb00112.x","article-title":"In vitro differentiation of mouse embryonic stem cells after activation by retinoic acid","volume":"15","author":"M Kawamorita","year":"2002","journal-title":"Hum Cell"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1016\/j.cell.2011.01.032","article-title":"Control of the embryonic stem cell state","volume":"144","author":"RA Young","year":"2011","journal-title":"Cell"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1039\/c1ib00045d","article-title":"Engineering 3D cell instructive microenvironments by rational assembly of artificial extracellular matrices and cell patterning","volume":"3","author":"A Sala","year":"2011","journal-title":"Integr Biol (Camb)"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"3244","DOI":"10.1016\/j.biomaterials.2010.01.039","article-title":"Extracellular matrix-mediated osteogenic differentiation of murine embryonic stem cells","volume":"31","author":"ND Evans","year":"2010","journal-title":"Biomaterials"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1042\/CBI20100452","article-title":"Gelatin induces trophectoderm differentiation of mouse embryonic stem cells","volume":"35","author":"S Peng","year":"2011","journal-title":"Cell Biol Int"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1073\/pnas.1103100109","article-title":"Attenuation of extrinsic signaling reveals the importance of matrix remodeling on maintenance of embryonic stem cell self-renewal","volume":"109","author":"LM Przybyla","year":"2012","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.22203\/eCM.v018a01","article-title":"Substrate stiffness affects early differentiation events in embryonic stem cells","volume":"18","author":"ND Evans","year":"2009","journal-title":"Eur Cell Mater"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1146\/annurev.bioeng.2.1.31","article-title":"Bioengineering models of cell signaling","volume":"2","author":"AR Asthagiri","year":"2000","journal-title":"Annu Rev Biomed Eng"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1039\/c0ib00141d","article-title":"Modeling and analysis of retinoic acid induced differentiation of uncommitted precursor cells","volume":"3","author":"R Tasseff","year":"2011","journal-title":"Integr Biol (Camb)"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1007\/978-1-4419-7210-1_14","article-title":"An ensemble approach for inferring semi-quantitative regulatory dynamics for the differentiation of mouse embryonic stem cells using prior knowledge","volume":"736","author":"D Lutter","year":"2012","journal-title":"Adv Exp Med Biol"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1515\/bmc.2011.008","article-title":"Embryonic stem cells: protein interaction networks","volume":"2","author":"PM Ng","year":"2011","journal-title":"Biomol Concepts"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1093\/bioinformatics\/16.8.707","article-title":"Genetic network inference: from co-expression clustering to reverse engineering","volume":"16","author":"P D'Haeseleer","year":"2000","journal-title":"Bioinformatics"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"4888","DOI":"10.1118\/1.3615164","article-title":"3D modeling of effects of increased oxygenation and activity concentration in tumors treated with radionuclides and antiangiogenic drugs","volume":"38","author":"JH Lagerlof","year":"2011","journal-title":"Med Phys"},{"key":"ref32","article-title":"Mass Transfer Limitations in Embryoid Bodies during Human Embryonic Stem Cell Differentiation","author":"AP Van Winkle","year":"2012","journal-title":"Cells Tissues Organs"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1002\/wsbm.75","article-title":"In silico models of cancer","volume":"2","author":"LB Edelman","year":"2010","journal-title":"Wiley Interdiscip Rev Syst Biol Med"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1109\/MEMB.2009.931790","article-title":"Multiscale modeling of cell mechanics and tissue organization","volume":"28","author":"T Beyer","year":"2009","journal-title":"IEEE Eng Med Biol Mag"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"88","DOI":"10.3389\/fimmu.2012.00088","article-title":"Selection of Mesenchymal-Like Metastatic Cells in Primary Tumors - An in silico Investigation","volume":"3","author":"V Narang","year":"2012","journal-title":"Front Immunol"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"e25306","DOI":"10.1371\/journal.pone.0025306","article-title":"Accounting for diffusion in agent based models of reaction-diffusion systems with application to cytoskeletal diffusion","volume":"6","author":"M Azimi","year":"2011","journal-title":"PLoS One"},{"key":"ref37","first-page":"145","article-title":"Agent based modeling of blood coagulation system: implementation using a GPU based high speed framework","volume":"2011","author":"W Chen","year":"2011","journal-title":"Conf Proc IEEE Eng Med Biol Soc"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1002\/bdrc.20106","article-title":"Agent-based modeling of multicell morphogenic processes during development","volume":"81","author":"BC Thorne","year":"2007","journal-title":"Birth Defects Res C Embryo Today"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1093\/bib\/bbm024","article-title":"Combining experiments with multi-cell agent-based modeling to study biological tissue patterning","volume":"8","author":"BC Thorne","year":"2007","journal-title":"Brief Bioinform"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1186\/1742-4682-8-46","article-title":"Developing a multiscale, multi-resolution agent-based brain tumor model by graphics processing units","volume":"8","author":"L Zhang","year":"2011","journal-title":"Theor Biol Med Model"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"20374","DOI":"10.1073\/pnas.0808725105","article-title":"Four-dimensional realistic modeling of pancreatic organogenesis","volume":"105","author":"Y Setty","year":"2008","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/1752-0509-3-13","article-title":"Elongation, proliferation &amp; migration differentiate endothelial cell phenotypes and determine capillary sprouting","volume":"3","author":"AA Qutub","year":"2009","journal-title":"BMC Syst Biol"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"3475","DOI":"10.1111\/j.1742-4658.2012.08646.x","article-title":"On the biomechanics of stem cell niche formation in the gut - modelling growing organoids","volume":"279","author":"P Buske","year":"2012","journal-title":"FEBS J"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"4219","DOI":"10.1242\/dev.003798","article-title":"Stochastic patterning in the mouse pre-implantation embryo","volume":"134","author":"JE Dietrich","year":"2007","journal-title":"Development"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"045007","DOI":"10.1088\/1478-3975\/8\/4\/045007","article-title":"Emergent cell and tissue dynamics from subcellular modeling of active biomechanical processes","volume":"8","author":"SA Sandersius","year":"2011","journal-title":"Phys Biol"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"3185","DOI":"10.1242\/dev.122.10.3185","article-title":"A role for cadherins in tissue formation","volume":"122","author":"L Larue","year":"1996","journal-title":"Development"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1634\/stemcells.2005-0112","article-title":"Shear-controlled single-step mouse embryonic stem cell expansion and embryoid body-based differentiation","volume":"23","author":"EY Fok","year":"2005","journal-title":"Stem Cells"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1016\/j.compbiomed.2008.04.002","article-title":"3D computational modeling and simulation of leukocyte rolling adhesion and deformation","volume":"38","author":"V Pappu","year":"2008","journal-title":"Comput Biol Med"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1038\/sj.cr.7290134","article-title":"Stem cell pluripotency and transcription factor Oct4","volume":"12","author":"GJ Pan","year":"2002","journal-title":"Cell Res"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/S0092-8674(00)81769-9","article-title":"Formation of pluripotent stem cells in the mammalian embryo depends on the POU transcription factor Oct4","volume":"95","author":"J Nichols","year":"1998","journal-title":"Cell"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"2900","DOI":"10.1073\/pnas.0308768101","article-title":"Multivariate proteomic analysis of murine embryonic stem cell self-renewal versus differentiation signaling","volume":"101","author":"W Prudhomme","year":"2004","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"e123","DOI":"10.1371\/journal.pcbi.0020123","article-title":"Transcriptional dynamics of the embryonic stem cell switch","volume":"2","author":"V Chickarmane","year":"2006","journal-title":"PLoS Comput Biol"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"1946","DOI":"10.1128\/MCB.01419-09","article-title":"Notch exhibits ligand bias and maneuvers stage-specific steering of neural differentiation in embryonic stem cells","volume":"30","author":"SK Ramasamy","year":"2010","journal-title":"Mol Cell Biol"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"2020","DOI":"10.1096\/fj.06-7852com","article-title":"LIF-mediated control of embryonic stem cell self-renewal emerges due to an autoregulatory loop","volume":"21","author":"RE Davey","year":"2007","journal-title":"FASEB J"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.jbiosc.2010.08.014","article-title":"Embryoid body culture of mouse embryonic stem cells using microwell and micropatterned chips","volume":"111","author":"Y Sakai","year":"2011","journal-title":"J Biosci Bioeng"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"e32975","DOI":"10.1371\/journal.pone.0032975","article-title":"Population based model of human embryonic stem cell (hESC) differentiation during endoderm induction","volume":"7","author":"K Task","year":"2012","journal-title":"PLoS One"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1093\/bioinformatics\/btq139","article-title":"An integer programming formulation to identify the sparse network architecture governing differentiation of embryonic stem cells","volume":"26","author":"I Banerjee","year":"2010","journal-title":"Bioinformatics"},{"key":"ref58","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1159\/000320572","article-title":"Portrayal of the Notch system in embryonic stem cell-derived embryoid bodies","volume":"193","author":"I Alcobia","year":"2011","journal-title":"Cells Tissues Organs"},{"key":"ref59","doi-asserted-by":"crossref","first-page":"3264","DOI":"10.1073\/pnas.1111478109","article-title":"Predictive microfluidic control of regulatory ligand trajectories in individual pluripotent cells","volume":"109","author":"F Moledina","year":"2012","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref60","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1002\/bit.22578","article-title":"Hydrodynamic modulation of embryonic stem cell differentiation by rotary orbital suspension culture","volume":"105","author":"CY Sargent","year":"2010","journal-title":"Biotechnol Bioeng"},{"key":"ref61","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1039\/c2ib00165a","article-title":"Systematic analysis of embryonic stem cell differentiation in hydrodynamic environments with controlled embryoid body size","volume":"4","author":"MA Kinney","year":"2012","journal-title":"Integr Biol (Camb)"},{"key":"ref62","doi-asserted-by":"crossref","first-page":"e1565","DOI":"10.1371\/journal.pone.0001565","article-title":"Reproducible, ultra high-throughput formation of multicellular organization from single cell suspension-derived human embryonic stem cell aggregates","volume":"3","author":"MD Ungrin","year":"2008","journal-title":"PLoS One"},{"key":"ref63","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.biomaterials.2010.08.113","article-title":"Incorporation of biomaterials in multicellular aggregates modulates pluripotent stem cell differentiation","volume":"32","author":"AM Bratt-Leal","year":"2011","journal-title":"Biomaterials"},{"key":"ref64","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.mbs.2012.08.004","article-title":"Stochastic modeling of stem-cell dynamics with control","volume":"240","author":"Z Sun","year":"2012","journal-title":"Math Biosci"}],"container-title":["PLoS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pcbi.1002952","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,11]],"date-time":"2022-02-11T13:54:56Z","timestamp":1644587696000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1002952"}},"subtitle":[],"editor":[{"given":"Stanislav","family":"Shvartsman","sequence":"first","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2013,3,14]]},"references-count":64,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2013,3,14]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1002952","relation":{},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,3,14]]}}}